Mark G. Kris, MD

This transcript has been edited for clarity.

Hello. It’s Mark Kris reporting back after attending the New York Lung Cancer Foundation Summit here in New York. A large amount of discussion went on, but as usual, I was most interested in the perioperative space.

In previous videos, I’ve talked about this ongoing discussion of whether you should operate and give adjuvant therapy or give neoadjuvant therapy, and I’ve addressed that already. One thing I want to bring up – and as we move off of that argument, which frankly doesn’t have an answer today, with neoadjuvant therapy, having all the data to support it – is what are the patterns of recurrence now that we have more successful systemic therapies, both targeted therapies and checkpoint inhibitors?

I was taught early on by my surgical mentors that the issue here was systemic control. While they could do very successful surgery to get high levels of local control, they could not control systemic disease. Sadly, the tools we had early on with chemotherapy were just not good enough. Suddenly, we have better tools to control systemic spread. In the past, the vast majority of occurrences were systemic; they’re now local.

What I think we need to do as a group of practitioners trying to deal with the problems getting in the way of curing our patients is look at what the issue is now. Frankly, the big issue now, as systemic therapy has controlled metastatic disease, is recurrence in the chest.

We give adjuvant osimertinib. Please remember what the numbers are. In the osimertinib arm, of the 11 recurrences reported in the European Society for Medical Oncology presentation a few years back, nine of them were in the chest or mediastinal nodes. In the arm that got no osimertinib afterward, there were 46 recurrences, and 32 of those 46 recurrences were in the chest, either the lung or mediastinal nodes. Therefore, 74% of the recurrences are suddenly in the chest. What’s the issue here?

The issue is we need to find strategies to give better disease control in the chest, as we have made inroads in controlling systemic disease with the targeted therapies in the endothelial growth factor receptor space, and very likely the checkpoint inhibitors, too, as that data kind of filters out. We need to think about how better to get local control.

I think rather than continue to get into this argument of neoadjuvant vs adjuvant, we should move to what’s really hurting our patients. Again, the data I quoted you was from the ADAURA trial, which was adjuvant therapy, and I’m sure the neoadjuvant is going to show the same thing. It’s better systemic therapy but now, more trouble in the chest.

How are we going to deal with that? I’d like to throw out one strategy, and that is to rethink the role of radiation in these patients. Again, if the problem is local in the chest, lung, and lymph nodes, we have to think about local therapy. Yes, we’re not recommending it routinely for everybody, but now that we have better systemic control, we need to rethink our options. The obvious one to rethink is about giving radiotherapy.

We should also use what we learned in the earlier trials, which is that there is harm in giving excessive radiation to the heart. If you avoid the heart, you avoid the harm. We have better planning strategies for stereotactic body radiotherapy and more traditional radiation, and of course, we have proton therapy as well.

As we continue to struggle with the idea of that patient with stage II or III disease, whether to give adjuvant vs neoadjuvant therapy, please remember to consider their risk in 2024. Their risk for first recurrence is in the chest.

What are we going to do to better control disease in the chest? We have a challenge. I’m sure we can meet it if we put our heads together.

Dr. Kris is professor of medicine at Weill Cornell Medical College, and attending physician, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York. He disclosed ties with AstraZeneca, Roche/Genentech, Ariad Pharmaceuticals, Pfizer, and PUMA.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Hello. It’s Mark Kris reporting back after attending the New York Lung Cancer Foundation Summit here in New York. A large amount of discussion went on, but as usual, I was most interested in the perioperative space.

In previous videos, I’ve talked about this ongoing discussion of whether you should operate and give adjuvant therapy or give neoadjuvant therapy, and I’ve addressed that already. One thing I want to bring up – and as we move off of that argument, which frankly doesn’t have an answer today, with neoadjuvant therapy, having all the data to support it – is what are the patterns of recurrence now that we have more successful systemic therapies, both targeted therapies and checkpoint inhibitors?

I was taught early on by my surgical mentors that the issue here was systemic control. While they could do very successful surgery to get high levels of local control, they could not control systemic disease. Sadly, the tools we had early on with chemotherapy were just not good enough. Suddenly, we have better tools to control systemic spread. In the past, the vast majority of occurrences were systemic; they’re now local.

What I think we need to do as a group of practitioners trying to deal with the problems getting in the way of curing our patients is look at what the issue is now. Frankly, the big issue now, as systemic therapy has controlled metastatic disease, is recurrence in the chest.

We give adjuvant osimertinib. Please remember what the numbers are. In the osimertinib arm, of the 11 recurrences reported in the European Society for Medical Oncology presentation a few years back, nine of them were in the chest or mediastinal nodes. In the arm that got no osimertinib afterward, there were 46 recurrences, and 32 of those 46 recurrences were in the chest, either the lung or mediastinal nodes. Therefore, 74% of the recurrences are suddenly in the chest. What’s the issue here?

The issue is we need to find strategies to give better disease control in the chest, as we have made inroads in controlling systemic disease with the targeted therapies in the endothelial growth factor receptor space, and very likely the checkpoint inhibitors, too, as that data kind of filters out. We need to think about how better to get local control.

I think rather than continue to get into this argument of neoadjuvant vs adjuvant, we should move to what’s really hurting our patients. Again, the data I quoted you was from the ADAURA trial, which was adjuvant therapy, and I’m sure the neoadjuvant is going to show the same thing. It’s better systemic therapy but now, more trouble in the chest.

How are we going to deal with that? I’d like to throw out one strategy, and that is to rethink the role of radiation in these patients. Again, if the problem is local in the chest, lung, and lymph nodes, we have to think about local therapy. Yes, we’re not recommending it routinely for everybody, but now that we have better systemic control, we need to rethink our options. The obvious one to rethink is about giving radiotherapy.

We should also use what we learned in the earlier trials, which is that there is harm in giving excessive radiation to the heart. If you avoid the heart, you avoid the harm. We have better planning strategies for stereotactic body radiotherapy and more traditional radiation, and of course, we have proton therapy as well.

As we continue to struggle with the idea of that patient with stage II or III disease, whether to give adjuvant vs neoadjuvant therapy, please remember to consider their risk in 2024. Their risk for first recurrence is in the chest.

What are we going to do to better control disease in the chest? We have a challenge. I’m sure we can meet it if we put our heads together.

Dr. Kris is professor of medicine at Weill Cornell Medical College, and attending physician, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York. He disclosed ties with AstraZeneca, Roche/Genentech, Ariad Pharmaceuticals, Pfizer, and PUMA.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Hello. It’s Mark Kris reporting back after attending the New York Lung Cancer Foundation Summit here in New York. A large amount of discussion went on, but as usual, I was most interested in the perioperative space.

In previous videos, I’ve talked about this ongoing discussion of whether you should operate and give adjuvant therapy or give neoadjuvant therapy, and I’ve addressed that already. One thing I want to bring up – and as we move off of that argument, which frankly doesn’t have an answer today, with neoadjuvant therapy, having all the data to support it – is what are the patterns of recurrence now that we have more successful systemic therapies, both targeted therapies and checkpoint inhibitors?

I was taught early on by my surgical mentors that the issue here was systemic control. While they could do very successful surgery to get high levels of local control, they could not control systemic disease. Sadly, the tools we had early on with chemotherapy were just not good enough. Suddenly, we have better tools to control systemic spread. In the past, the vast majority of occurrences were systemic; they’re now local.

What I think we need to do as a group of practitioners trying to deal with the problems getting in the way of curing our patients is look at what the issue is now. Frankly, the big issue now, as systemic therapy has controlled metastatic disease, is recurrence in the chest.

We give adjuvant osimertinib. Please remember what the numbers are. In the osimertinib arm, of the 11 recurrences reported in the European Society for Medical Oncology presentation a few years back, nine of them were in the chest or mediastinal nodes. In the arm that got no osimertinib afterward, there were 46 recurrences, and 32 of those 46 recurrences were in the chest, either the lung or mediastinal nodes. Therefore, 74% of the recurrences are suddenly in the chest. What’s the issue here?

The issue is we need to find strategies to give better disease control in the chest, as we have made inroads in controlling systemic disease with the targeted therapies in the endothelial growth factor receptor space, and very likely the checkpoint inhibitors, too, as that data kind of filters out. We need to think about how better to get local control.

I think rather than continue to get into this argument of neoadjuvant vs adjuvant, we should move to what’s really hurting our patients. Again, the data I quoted you was from the ADAURA trial, which was adjuvant therapy, and I’m sure the neoadjuvant is going to show the same thing. It’s better systemic therapy but now, more trouble in the chest.

How are we going to deal with that? I’d like to throw out one strategy, and that is to rethink the role of radiation in these patients. Again, if the problem is local in the chest, lung, and lymph nodes, we have to think about local therapy. Yes, we’re not recommending it routinely for everybody, but now that we have better systemic control, we need to rethink our options. The obvious one to rethink is about giving radiotherapy.

We should also use what we learned in the earlier trials, which is that there is harm in giving excessive radiation to the heart. If you avoid the heart, you avoid the harm. We have better planning strategies for stereotactic body radiotherapy and more traditional radiation, and of course, we have proton therapy as well.

As we continue to struggle with the idea of that patient with stage II or III disease, whether to give adjuvant vs neoadjuvant therapy, please remember to consider their risk in 2024. Their risk for first recurrence is in the chest.

What are we going to do to better control disease in the chest? We have a challenge. I’m sure we can meet it if we put our heads together.

Dr. Kris is professor of medicine at Weill Cornell Medical College, and attending physician, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York. He disclosed ties with AstraZeneca, Roche/Genentech, Ariad Pharmaceuticals, Pfizer, and PUMA.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

I’ve been spending time recently reflecting on the biggest developments from last year. I have to say that the breakthrough of the year, based on the amount of data presented and the importance of the data, is chemotherapy. I never thought I would say that. Many folks have tried to relegate chemotherapy to the museum, but last year it came to the forefront.

Let’s start with neoadjuvant therapy. We now have multiple drug approvals for giving a checkpoint inhibitor and neoadjuvant therapy in what I would say is a new standard of care for patients with locally advanced lung cancers who are candidates for surgery. In all those trials, there was a clear improvement in progression-free survival by adding a checkpoint inhibitor to chemotherapy. The cornerstone of this regimen is chemotherapy.

What about adjuvant therapy? I think one of the most astounding pieces of data last year was in the adjuvant realm. In the trial comparing adjuvant osimertinib with placebo in patients with EGFR-mutant disease, patients who received chemotherapy in addition to osimertinib had a 7% improvement in 5-year survival. Patients who had placebo, who got chemotherapy vs didn’t, had a 9% improvement in 5-year survival. Those are huge numbers for that kind of metric, and it happened with chemotherapy.

What about targeted therapies? Again, I think people were astounded that, by adding chemotherapy to osimertinib compared with osimertinib alone, there was a 9-month improvement overall in progression-free survival. I think in the presentation of the data that has been made, the most remarkable piece of data is that, in patients with brain metastases, chemotherapy on top of osimertinib improved progression-free survival. Not only did it improve progression-free survival, but it did it with brain metastases, where people think it just doesn’t help at all.

What about other, newer agents with chemotherapy? Amivantamab, I would say, has hitched itself to chemotherapy. A trial in EGFR exon 20 compared chemo to amivantamab plus chemotherapy. There again, chemo is the common denominator. Amivantamab added approximately 5 months of improved progression-free survival. Again, chemo was used. In adjuvant, neoadjuvant, and targeted therapies, chemotherapy adds.

What about the second line? I think everybody was very disappointed when second-line sotorasib gave a very tiny amount of progression-free survival improvement over docetaxel. I think we all want more for our patients than we can deliver with docetaxel. The roughly 5-week improvement seen with sotorasib was one that raised a question about the place of sotorasib in this setting.

Clearly, we’ve all seen patients have an excellent result with sotorasib as an additional option for treating patients with long progression-free survival, high rates of response, and good tolerability even at the 960 mg dose. But in the randomized trial, it wasn’t better than docetaxel. Again, I think we were disappointed with tusamitamab ravtansine in that it could not beat docetaxel either. I think the idea here is that chemo still has a huge place and still remains the treatment that we have to beat.

We’re all very excited about the antibody-drug conjugates and I think everybody sees them as another advance. Many folks have said that they are just a more precise way of delivering chemotherapy, and when you look at the side effects, it supports that — they’re largely side effects of chemotherapy with these drugs across the board. Also, when you look at the patterns of resistance, the resistance really isn’t a resistance to the targeted therapy; it’s a resistance to chemotherapy more than anything else.

So we’re happy that the antibody-drug conjugates are available and we were disappointed with tusamitamab ravtansine because we thought that it could beat docetaxel. But in truth, it didn’t, and unfortunately, that pivotal trial led to the end of the entire development program for that agent, as stated in a press release.

The molecule or treatment of the year is chemotherapy — added to targeted therapies, used with immunotherapy, and now attached to antibodies as part of antibody-drug conjugates. I think it remains, more than any one treatment, a very effective treatment for patients and deserves to be used.

There are a lot of choices here. I think you have to be very careful to choose wisely, and you also have to be careful because chemotherapy has side effects. The nice thing is that many of those side effects can be ameliorated. We have to make sure that we use all the supportive medications we can.

Who would have thought that chemotherapy would be the treatment of the year in 2023 for lung cancers?
 

Dr. Kris is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York City. He disclosed ties with AstraZeneca, Roche/Genentech, Ariad Pharmaceuticals, Pfizer Inc, and PUMA.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

I’ve been spending time recently reflecting on the biggest developments from last year. I have to say that the breakthrough of the year, based on the amount of data presented and the importance of the data, is chemotherapy. I never thought I would say that. Many folks have tried to relegate chemotherapy to the museum, but last year it came to the forefront.

Let’s start with neoadjuvant therapy. We now have multiple drug approvals for giving a checkpoint inhibitor and neoadjuvant therapy in what I would say is a new standard of care for patients with locally advanced lung cancers who are candidates for surgery. In all those trials, there was a clear improvement in progression-free survival by adding a checkpoint inhibitor to chemotherapy. The cornerstone of this regimen is chemotherapy.

What about adjuvant therapy? I think one of the most astounding pieces of data last year was in the adjuvant realm. In the trial comparing adjuvant osimertinib with placebo in patients with EGFR-mutant disease, patients who received chemotherapy in addition to osimertinib had a 7% improvement in 5-year survival. Patients who had placebo, who got chemotherapy vs didn’t, had a 9% improvement in 5-year survival. Those are huge numbers for that kind of metric, and it happened with chemotherapy.

What about targeted therapies? Again, I think people were astounded that, by adding chemotherapy to osimertinib compared with osimertinib alone, there was a 9-month improvement overall in progression-free survival. I think in the presentation of the data that has been made, the most remarkable piece of data is that, in patients with brain metastases, chemotherapy on top of osimertinib improved progression-free survival. Not only did it improve progression-free survival, but it did it with brain metastases, where people think it just doesn’t help at all.

What about other, newer agents with chemotherapy? Amivantamab, I would say, has hitched itself to chemotherapy. A trial in EGFR exon 20 compared chemo to amivantamab plus chemotherapy. There again, chemo is the common denominator. Amivantamab added approximately 5 months of improved progression-free survival. Again, chemo was used. In adjuvant, neoadjuvant, and targeted therapies, chemotherapy adds.

What about the second line? I think everybody was very disappointed when second-line sotorasib gave a very tiny amount of progression-free survival improvement over docetaxel. I think we all want more for our patients than we can deliver with docetaxel. The roughly 5-week improvement seen with sotorasib was one that raised a question about the place of sotorasib in this setting.

Clearly, we’ve all seen patients have an excellent result with sotorasib as an additional option for treating patients with long progression-free survival, high rates of response, and good tolerability even at the 960 mg dose. But in the randomized trial, it wasn’t better than docetaxel. Again, I think we were disappointed with tusamitamab ravtansine in that it could not beat docetaxel either. I think the idea here is that chemo still has a huge place and still remains the treatment that we have to beat.

We’re all very excited about the antibody-drug conjugates and I think everybody sees them as another advance. Many folks have said that they are just a more precise way of delivering chemotherapy, and when you look at the side effects, it supports that — they’re largely side effects of chemotherapy with these drugs across the board. Also, when you look at the patterns of resistance, the resistance really isn’t a resistance to the targeted therapy; it’s a resistance to chemotherapy more than anything else.

So we’re happy that the antibody-drug conjugates are available and we were disappointed with tusamitamab ravtansine because we thought that it could beat docetaxel. But in truth, it didn’t, and unfortunately, that pivotal trial led to the end of the entire development program for that agent, as stated in a press release.

The molecule or treatment of the year is chemotherapy — added to targeted therapies, used with immunotherapy, and now attached to antibodies as part of antibody-drug conjugates. I think it remains, more than any one treatment, a very effective treatment for patients and deserves to be used.

There are a lot of choices here. I think you have to be very careful to choose wisely, and you also have to be careful because chemotherapy has side effects. The nice thing is that many of those side effects can be ameliorated. We have to make sure that we use all the supportive medications we can.

Who would have thought that chemotherapy would be the treatment of the year in 2023 for lung cancers?
 

Dr. Kris is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York City. He disclosed ties with AstraZeneca, Roche/Genentech, Ariad Pharmaceuticals, Pfizer Inc, and PUMA.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

I’ve been spending time recently reflecting on the biggest developments from last year. I have to say that the breakthrough of the year, based on the amount of data presented and the importance of the data, is chemotherapy. I never thought I would say that. Many folks have tried to relegate chemotherapy to the museum, but last year it came to the forefront.

Let’s start with neoadjuvant therapy. We now have multiple drug approvals for giving a checkpoint inhibitor and neoadjuvant therapy in what I would say is a new standard of care for patients with locally advanced lung cancers who are candidates for surgery. In all those trials, there was a clear improvement in progression-free survival by adding a checkpoint inhibitor to chemotherapy. The cornerstone of this regimen is chemotherapy.

What about adjuvant therapy? I think one of the most astounding pieces of data last year was in the adjuvant realm. In the trial comparing adjuvant osimertinib with placebo in patients with EGFR-mutant disease, patients who received chemotherapy in addition to osimertinib had a 7% improvement in 5-year survival. Patients who had placebo, who got chemotherapy vs didn’t, had a 9% improvement in 5-year survival. Those are huge numbers for that kind of metric, and it happened with chemotherapy.

What about targeted therapies? Again, I think people were astounded that, by adding chemotherapy to osimertinib compared with osimertinib alone, there was a 9-month improvement overall in progression-free survival. I think in the presentation of the data that has been made, the most remarkable piece of data is that, in patients with brain metastases, chemotherapy on top of osimertinib improved progression-free survival. Not only did it improve progression-free survival, but it did it with brain metastases, where people think it just doesn’t help at all.

What about other, newer agents with chemotherapy? Amivantamab, I would say, has hitched itself to chemotherapy. A trial in EGFR exon 20 compared chemo to amivantamab plus chemotherapy. There again, chemo is the common denominator. Amivantamab added approximately 5 months of improved progression-free survival. Again, chemo was used. In adjuvant, neoadjuvant, and targeted therapies, chemotherapy adds.

What about the second line? I think everybody was very disappointed when second-line sotorasib gave a very tiny amount of progression-free survival improvement over docetaxel. I think we all want more for our patients than we can deliver with docetaxel. The roughly 5-week improvement seen with sotorasib was one that raised a question about the place of sotorasib in this setting.

Clearly, we’ve all seen patients have an excellent result with sotorasib as an additional option for treating patients with long progression-free survival, high rates of response, and good tolerability even at the 960 mg dose. But in the randomized trial, it wasn’t better than docetaxel. Again, I think we were disappointed with tusamitamab ravtansine in that it could not beat docetaxel either. I think the idea here is that chemo still has a huge place and still remains the treatment that we have to beat.

We’re all very excited about the antibody-drug conjugates and I think everybody sees them as another advance. Many folks have said that they are just a more precise way of delivering chemotherapy, and when you look at the side effects, it supports that — they’re largely side effects of chemotherapy with these drugs across the board. Also, when you look at the patterns of resistance, the resistance really isn’t a resistance to the targeted therapy; it’s a resistance to chemotherapy more than anything else.

So we’re happy that the antibody-drug conjugates are available and we were disappointed with tusamitamab ravtansine because we thought that it could beat docetaxel. But in truth, it didn’t, and unfortunately, that pivotal trial led to the end of the entire development program for that agent, as stated in a press release.

The molecule or treatment of the year is chemotherapy — added to targeted therapies, used with immunotherapy, and now attached to antibodies as part of antibody-drug conjugates. I think it remains, more than any one treatment, a very effective treatment for patients and deserves to be used.

There are a lot of choices here. I think you have to be very careful to choose wisely, and you also have to be careful because chemotherapy has side effects. The nice thing is that many of those side effects can be ameliorated. We have to make sure that we use all the supportive medications we can.

Who would have thought that chemotherapy would be the treatment of the year in 2023 for lung cancers?
 

Dr. Kris is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York City. He disclosed ties with AstraZeneca, Roche/Genentech, Ariad Pharmaceuticals, Pfizer Inc, and PUMA.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

I’ve been thinking lately about treatments after initial therapy for non–small cell lung cancers, what people often call second-line therapy.

I think the first thought is that, for all the regimens that are available and tested, the results are clearly not as good as seen with first-line therapy. I’ll get into some specifics in a second. That being the case, it’s really important to make the best choice for first-line therapy.

The second thing that is absolutely critical is to very carefully assess when that first-line therapy has stopped working and whether there is a need for a new systemic therapy. We very often have these situations where there is an oligoprogression, and by treating a single symptomatic lesion, you may get the patient in a very good place and may continue initial therapy. Very often, there is inconsequential growth of the cancer.

For example, if there is a 21% increase in the size of a primary tumor that is not associated with any symptoms in a person who is living their life and is not having any severe side effects, you have to think long and hard about changing that therapy. I wouldn’t even give a consolidative therapy there if they’re really doing well. Obviously, consolidative therapies are a new therapy, and they have their side effects with them as well.

Please think really carefully and weigh all factors, from the patient, the toxicity, and the benefit, before changing the initial systemic therapy. I would continue it as long as possible.

With second-line therapy, sadly, none of them have a huge benefit anywhere near what we see in first line. All the rates of response are well under 50%. Just getting into it, you’re not going to shrink the cancer by more than 30% in the majority of patients, so you have to think long and hard about making that switch.

Second, our standard still remains docetaxel, and the numbers on docetaxel are really not great. It’s about a 15% rate of response and a median survival of about 5 months. Now, by adding other RET drugs to docetaxel, you can achieve better results. By adding ramucirumab, for example, the response rate just about doubles and the duration of response and progression-free survival both go up by a few months.

For patients who have KRAS G12C, in the randomized trial that has been done so far, over docetaxel, you get, again, a doubling of response. For patients where response is important, you really double that response rate, but also you get an improvement in median progression-free survival by, again, 2-3 months. There is benefit there in terms of response and progression-free survival; however, it’s not huge.

Please remember, if you’re choosing to use docetaxel, to think about using alternative dosages and schedules. When you look at the course of a person treated with docetaxel over, let’s say, a 6-month period, you often see that doses are held. When you look at the total dose, it’s very similar to an every-2-week dose of a lower amount. I routinely give a 60-mg flat dose every 2 weeks.

I urge you to look at the progress of one of your patients over a 6-month period who was given the 75-mg dose. Many of those doses end up getting held. When all is said and done, you give a lower dose over that whole time from that 75-mg dose. Giving 35 mg/m² or a 60-mg flat dose every 2 weeks, you end up getting almost exactly the same amount of docetaxel. There’s really no convincing evidence that the higher dose is better. It’s clearly harder on the patient.

I’ve shared some thoughts about second-line therapy. We really have to do better. Please make sure that your first-line therapy is the best you can give. Make sure you’ve gotten everything out of that first-line therapy and that it will be continued as long as possible, as long as you and the patient have concluded that there’s benefit. When you do switch, try to give the most effective regimen that you have, which would be docetaxel with ramucirumab, or for patients with KRAS G12C, giving adagrasib or sotorasib at this point.

Dr. Kris is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York. He reported conflicts of interest with AstraZeneca, Roche/Genentech, Ariad Pharmaceuticals, Pfizer, and PUMA.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

I’ve been thinking lately about treatments after initial therapy for non–small cell lung cancers, what people often call second-line therapy.

I think the first thought is that, for all the regimens that are available and tested, the results are clearly not as good as seen with first-line therapy. I’ll get into some specifics in a second. That being the case, it’s really important to make the best choice for first-line therapy.

The second thing that is absolutely critical is to very carefully assess when that first-line therapy has stopped working and whether there is a need for a new systemic therapy. We very often have these situations where there is an oligoprogression, and by treating a single symptomatic lesion, you may get the patient in a very good place and may continue initial therapy. Very often, there is inconsequential growth of the cancer.

For example, if there is a 21% increase in the size of a primary tumor that is not associated with any symptoms in a person who is living their life and is not having any severe side effects, you have to think long and hard about changing that therapy. I wouldn’t even give a consolidative therapy there if they’re really doing well. Obviously, consolidative therapies are a new therapy, and they have their side effects with them as well.

Please think really carefully and weigh all factors, from the patient, the toxicity, and the benefit, before changing the initial systemic therapy. I would continue it as long as possible.

With second-line therapy, sadly, none of them have a huge benefit anywhere near what we see in first line. All the rates of response are well under 50%. Just getting into it, you’re not going to shrink the cancer by more than 30% in the majority of patients, so you have to think long and hard about making that switch.

Second, our standard still remains docetaxel, and the numbers on docetaxel are really not great. It’s about a 15% rate of response and a median survival of about 5 months. Now, by adding other RET drugs to docetaxel, you can achieve better results. By adding ramucirumab, for example, the response rate just about doubles and the duration of response and progression-free survival both go up by a few months.

For patients who have KRAS G12C, in the randomized trial that has been done so far, over docetaxel, you get, again, a doubling of response. For patients where response is important, you really double that response rate, but also you get an improvement in median progression-free survival by, again, 2-3 months. There is benefit there in terms of response and progression-free survival; however, it’s not huge.

Please remember, if you’re choosing to use docetaxel, to think about using alternative dosages and schedules. When you look at the course of a person treated with docetaxel over, let’s say, a 6-month period, you often see that doses are held. When you look at the total dose, it’s very similar to an every-2-week dose of a lower amount. I routinely give a 60-mg flat dose every 2 weeks.

I urge you to look at the progress of one of your patients over a 6-month period who was given the 75-mg dose. Many of those doses end up getting held. When all is said and done, you give a lower dose over that whole time from that 75-mg dose. Giving 35 mg/m² or a 60-mg flat dose every 2 weeks, you end up getting almost exactly the same amount of docetaxel. There’s really no convincing evidence that the higher dose is better. It’s clearly harder on the patient.

I’ve shared some thoughts about second-line therapy. We really have to do better. Please make sure that your first-line therapy is the best you can give. Make sure you’ve gotten everything out of that first-line therapy and that it will be continued as long as possible, as long as you and the patient have concluded that there’s benefit. When you do switch, try to give the most effective regimen that you have, which would be docetaxel with ramucirumab, or for patients with KRAS G12C, giving adagrasib or sotorasib at this point.

Dr. Kris is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York. He reported conflicts of interest with AstraZeneca, Roche/Genentech, Ariad Pharmaceuticals, Pfizer, and PUMA.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

I’ve been thinking lately about treatments after initial therapy for non–small cell lung cancers, what people often call second-line therapy.

I think the first thought is that, for all the regimens that are available and tested, the results are clearly not as good as seen with first-line therapy. I’ll get into some specifics in a second. That being the case, it’s really important to make the best choice for first-line therapy.

The second thing that is absolutely critical is to very carefully assess when that first-line therapy has stopped working and whether there is a need for a new systemic therapy. We very often have these situations where there is an oligoprogression, and by treating a single symptomatic lesion, you may get the patient in a very good place and may continue initial therapy. Very often, there is inconsequential growth of the cancer.

For example, if there is a 21% increase in the size of a primary tumor that is not associated with any symptoms in a person who is living their life and is not having any severe side effects, you have to think long and hard about changing that therapy. I wouldn’t even give a consolidative therapy there if they’re really doing well. Obviously, consolidative therapies are a new therapy, and they have their side effects with them as well.

Please think really carefully and weigh all factors, from the patient, the toxicity, and the benefit, before changing the initial systemic therapy. I would continue it as long as possible.

With second-line therapy, sadly, none of them have a huge benefit anywhere near what we see in first line. All the rates of response are well under 50%. Just getting into it, you’re not going to shrink the cancer by more than 30% in the majority of patients, so you have to think long and hard about making that switch.

Second, our standard still remains docetaxel, and the numbers on docetaxel are really not great. It’s about a 15% rate of response and a median survival of about 5 months. Now, by adding other RET drugs to docetaxel, you can achieve better results. By adding ramucirumab, for example, the response rate just about doubles and the duration of response and progression-free survival both go up by a few months.

For patients who have KRAS G12C, in the randomized trial that has been done so far, over docetaxel, you get, again, a doubling of response. For patients where response is important, you really double that response rate, but also you get an improvement in median progression-free survival by, again, 2-3 months. There is benefit there in terms of response and progression-free survival; however, it’s not huge.

Please remember, if you’re choosing to use docetaxel, to think about using alternative dosages and schedules. When you look at the course of a person treated with docetaxel over, let’s say, a 6-month period, you often see that doses are held. When you look at the total dose, it’s very similar to an every-2-week dose of a lower amount. I routinely give a 60-mg flat dose every 2 weeks.

I urge you to look at the progress of one of your patients over a 6-month period who was given the 75-mg dose. Many of those doses end up getting held. When all is said and done, you give a lower dose over that whole time from that 75-mg dose. Giving 35 mg/m² or a 60-mg flat dose every 2 weeks, you end up getting almost exactly the same amount of docetaxel. There’s really no convincing evidence that the higher dose is better. It’s clearly harder on the patient.

I’ve shared some thoughts about second-line therapy. We really have to do better. Please make sure that your first-line therapy is the best you can give. Make sure you’ve gotten everything out of that first-line therapy and that it will be continued as long as possible, as long as you and the patient have concluded that there’s benefit. When you do switch, try to give the most effective regimen that you have, which would be docetaxel with ramucirumab, or for patients with KRAS G12C, giving adagrasib or sotorasib at this point.

Dr. Kris is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York. He reported conflicts of interest with AstraZeneca, Roche/Genentech, Ariad Pharmaceuticals, Pfizer, and PUMA.

A version of this article first appeared on Medscape.com.

I’m speaking today about the ever-rising prominence of neoadjuvant therapy for patients with locally advanced lung cancers. There are more and more data emerging suggesting that the neoadjuvant strategy is a better one.

Many of you saw the press release from Merck announcing that their randomized trial comparing chemo with chemo plus pembrolizumab in the neoadjuvant setting led to improved event-free survival and also improved pathologic complete response rate.

This comes in addition to the data from the AstraZeneca trial with durvalumab saying they’ve already achieved their endpoint of higher pathologic complete response rate vs. chemotherapy alone and also the data with nivolumab from Bristol-Myers Squibb saying that nivolumab plus chemotherapy leads to a better event-free survival and a better pathologic complete response rate. That information has led to Food and Drug Administration approval for their regimen.

We’re running the table with these very positive data, and I think it’s just a sign that the approach is safe and effective.

A huge question has come up. I just came from a meeting of lung cancer experts asking what to do if you have a patient with a small tumor, for example, a 3-cm tumor. Do you recommend immediate surgery followed by adjuvant therapy, chemotherapy, and then a checkpoint inhibitor if appropriate? Or do you proceed with neoadjuvant therapy if appropriate? The truth is that it’s a very difficult decision.

We have overwhelming data that the neoadjuvant approach works for that patient. Please remember that this is a clinically staged patient. This is not the patient after their surgery, where I think we have a very clear path. We have adjuvant data and adjuvant trials for those patients.

For the patient who’s in your office with a small tumor or a small tumor and only hilar lymphadenopathy, the decision there isn’t data driven, but rather it is experience driven. The data that are out there right now suggest that neoadjuvant therapy is a better way to go. Why is that?

Well, I think that the first reason is that it is probably a better regimen. I think many of you saw the recent clinical trial by Patel and colleagues in the New England Journal of Medicine with melanoma. It was an interesting trial. They gave a checkpoint inhibitor for 18 doses after surgery for melanoma versus three doses of checkpoint inhibitor, surgery, and then 15 doses of the checkpoint inhibitor.

It was 18 doses versus 18 doses, with the only difference being the three doses before surgery. Lo and behold, the three doses before surgery led to a better event-free survival.

There are preclinical data in lung cancer demonstrating that the same thing is true. Tina Cascone published on that years ago. We could talk about why, but it appears that neoadjuvant is just better.

There are other advantages to it as well. I think a big one is that all the information shows that it’s better tolerated, so you’re more likely to give all the drug. You can see if the drug isn’t working, and you can stop the drug. Also, if the drug is causing a side effect, you can see whether it’s working or not and use that decision to stop. It’s different than when you’re giving a drug in the adjuvant setting where you don’t really know whether it is working or not.

I think that it’s time to change some of our standards. When patients appear with lung cancers other than tiny ones that might be detected through screening, you need to convene your multidisciplinary group. You need to weigh the pros and cons I think that it’s time to change some of our standards. When patients appear with lung cancers other than tiny ones that might be detected through screening, you need to convene your multidisciplinary group coming in. It’s already an FDA-approved regimen with nivolumab and chemotherapy, and I think we’re moving to making that our standard of care now.

The way to handle it today, though, is to convene your multidisciplinary panel about every patient other than those with the tiniest of lung cancers and put your heads together to see what the best treatment is for that patient.

Dr. Kris is professor of medicine, Weill Cornell Medicine, and the William and Joy Ruane Chair in Thoracic Oncology, Memorial Sloan Kettering Cancer Center, both in New York. He disclosed ties with Ariad Pharmaceuticals, AstraZeneca, Pfizer, PUMA, and Roche/Genentech.

A version of this article appeared on Medscape.com.

I’m speaking today about the ever-rising prominence of neoadjuvant therapy for patients with locally advanced lung cancers. There are more and more data emerging suggesting that the neoadjuvant strategy is a better one.

Many of you saw the press release from Merck announcing that their randomized trial comparing chemo with chemo plus pembrolizumab in the neoadjuvant setting led to improved event-free survival and also improved pathologic complete response rate.

This comes in addition to the data from the AstraZeneca trial with durvalumab saying they’ve already achieved their endpoint of higher pathologic complete response rate vs. chemotherapy alone and also the data with nivolumab from Bristol-Myers Squibb saying that nivolumab plus chemotherapy leads to a better event-free survival and a better pathologic complete response rate. That information has led to Food and Drug Administration approval for their regimen.

We’re running the table with these very positive data, and I think it’s just a sign that the approach is safe and effective.

A huge question has come up. I just came from a meeting of lung cancer experts asking what to do if you have a patient with a small tumor, for example, a 3-cm tumor. Do you recommend immediate surgery followed by adjuvant therapy, chemotherapy, and then a checkpoint inhibitor if appropriate? Or do you proceed with neoadjuvant therapy if appropriate? The truth is that it’s a very difficult decision.

We have overwhelming data that the neoadjuvant approach works for that patient. Please remember that this is a clinically staged patient. This is not the patient after their surgery, where I think we have a very clear path. We have adjuvant data and adjuvant trials for those patients.

For the patient who’s in your office with a small tumor or a small tumor and only hilar lymphadenopathy, the decision there isn’t data driven, but rather it is experience driven. The data that are out there right now suggest that neoadjuvant therapy is a better way to go. Why is that?

Well, I think that the first reason is that it is probably a better regimen. I think many of you saw the recent clinical trial by Patel and colleagues in the New England Journal of Medicine with melanoma. It was an interesting trial. They gave a checkpoint inhibitor for 18 doses after surgery for melanoma versus three doses of checkpoint inhibitor, surgery, and then 15 doses of the checkpoint inhibitor.

It was 18 doses versus 18 doses, with the only difference being the three doses before surgery. Lo and behold, the three doses before surgery led to a better event-free survival.

There are preclinical data in lung cancer demonstrating that the same thing is true. Tina Cascone published on that years ago. We could talk about why, but it appears that neoadjuvant is just better.

There are other advantages to it as well. I think a big one is that all the information shows that it’s better tolerated, so you’re more likely to give all the drug. You can see if the drug isn’t working, and you can stop the drug. Also, if the drug is causing a side effect, you can see whether it’s working or not and use that decision to stop. It’s different than when you’re giving a drug in the adjuvant setting where you don’t really know whether it is working or not.

I think that it’s time to change some of our standards. When patients appear with lung cancers other than tiny ones that might be detected through screening, you need to convene your multidisciplinary group. You need to weigh the pros and cons I think that it’s time to change some of our standards. When patients appear with lung cancers other than tiny ones that might be detected through screening, you need to convene your multidisciplinary group coming in. It’s already an FDA-approved regimen with nivolumab and chemotherapy, and I think we’re moving to making that our standard of care now.

The way to handle it today, though, is to convene your multidisciplinary panel about every patient other than those with the tiniest of lung cancers and put your heads together to see what the best treatment is for that patient.

Dr. Kris is professor of medicine, Weill Cornell Medicine, and the William and Joy Ruane Chair in Thoracic Oncology, Memorial Sloan Kettering Cancer Center, both in New York. He disclosed ties with Ariad Pharmaceuticals, AstraZeneca, Pfizer, PUMA, and Roche/Genentech.

A version of this article appeared on Medscape.com.

I’m speaking today about the ever-rising prominence of neoadjuvant therapy for patients with locally advanced lung cancers. There are more and more data emerging suggesting that the neoadjuvant strategy is a better one.

Many of you saw the press release from Merck announcing that their randomized trial comparing chemo with chemo plus pembrolizumab in the neoadjuvant setting led to improved event-free survival and also improved pathologic complete response rate.

This comes in addition to the data from the AstraZeneca trial with durvalumab saying they’ve already achieved their endpoint of higher pathologic complete response rate vs. chemotherapy alone and also the data with nivolumab from Bristol-Myers Squibb saying that nivolumab plus chemotherapy leads to a better event-free survival and a better pathologic complete response rate. That information has led to Food and Drug Administration approval for their regimen.

We’re running the table with these very positive data, and I think it’s just a sign that the approach is safe and effective.

A huge question has come up. I just came from a meeting of lung cancer experts asking what to do if you have a patient with a small tumor, for example, a 3-cm tumor. Do you recommend immediate surgery followed by adjuvant therapy, chemotherapy, and then a checkpoint inhibitor if appropriate? Or do you proceed with neoadjuvant therapy if appropriate? The truth is that it’s a very difficult decision.

We have overwhelming data that the neoadjuvant approach works for that patient. Please remember that this is a clinically staged patient. This is not the patient after their surgery, where I think we have a very clear path. We have adjuvant data and adjuvant trials for those patients.

For the patient who’s in your office with a small tumor or a small tumor and only hilar lymphadenopathy, the decision there isn’t data driven, but rather it is experience driven. The data that are out there right now suggest that neoadjuvant therapy is a better way to go. Why is that?

Well, I think that the first reason is that it is probably a better regimen. I think many of you saw the recent clinical trial by Patel and colleagues in the New England Journal of Medicine with melanoma. It was an interesting trial. They gave a checkpoint inhibitor for 18 doses after surgery for melanoma versus three doses of checkpoint inhibitor, surgery, and then 15 doses of the checkpoint inhibitor.

It was 18 doses versus 18 doses, with the only difference being the three doses before surgery. Lo and behold, the three doses before surgery led to a better event-free survival.

There are preclinical data in lung cancer demonstrating that the same thing is true. Tina Cascone published on that years ago. We could talk about why, but it appears that neoadjuvant is just better.

There are other advantages to it as well. I think a big one is that all the information shows that it’s better tolerated, so you’re more likely to give all the drug. You can see if the drug isn’t working, and you can stop the drug. Also, if the drug is causing a side effect, you can see whether it’s working or not and use that decision to stop. It’s different than when you’re giving a drug in the adjuvant setting where you don’t really know whether it is working or not.

I think that it’s time to change some of our standards. When patients appear with lung cancers other than tiny ones that might be detected through screening, you need to convene your multidisciplinary group. You need to weigh the pros and cons I think that it’s time to change some of our standards. When patients appear with lung cancers other than tiny ones that might be detected through screening, you need to convene your multidisciplinary group coming in. It’s already an FDA-approved regimen with nivolumab and chemotherapy, and I think we’re moving to making that our standard of care now.

The way to handle it today, though, is to convene your multidisciplinary panel about every patient other than those with the tiniest of lung cancers and put your heads together to see what the best treatment is for that patient.

Dr. Kris is professor of medicine, Weill Cornell Medicine, and the William and Joy Ruane Chair in Thoracic Oncology, Memorial Sloan Kettering Cancer Center, both in New York. He disclosed ties with Ariad Pharmaceuticals, AstraZeneca, Pfizer, PUMA, and Roche/Genentech.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Hello. It’s Mark Kris from Memorial Sloan-Kettering, still musing on things I learned at ASCO 2023.

I learned that there is a new C word.

People used to be afraid to use the word “cancer,” so they would call it the C word. Hopefully we’ve gotten over that stigma, that cancer is an illness that can be fought like any other illness.

There’s a new C word now that people seem, again, afraid to use, and that word is “cure.” It’s almost a true rarity that – again, I’m talking about the lung cancer world in particular – folks use the word “cure.” I didn’t hear it at ASCO, but the truth of the matter is that’s a word we should be using and be using more.

What do our patients want? I think if you truly ask a patient what their goal of care should be, it would be to cure the illness. What I mean by “cure” is to eradicate the cancer that is in their body, keep the cancer and its effects from interfering with their ability to continue their lives, and to do it for the length of their natural life. That’s what our patients want. Yes, overall survival is important, but not as much as a life free of cancer and the burden that it puts on people having cancer in the body.

When you start thinking about cure and how to make it a goal of care, a number of issues immediately crop up. The first one is defining what is meant by “cure.” We don’t have a strict definition of cure. Again, I would probably go to the patients and ask them what they mean by it. There may be some landmark part of the definition that needs to be discussed and addressed, but again, to me it’s having your life not disturbed by cancer, and that generally comes by eradicating cancer. Living with cancer is harder than the living after cancer has been cured. But we don’t have a good definition.

We also don’t have a good way of designing clinical trials to assess whether the regimen is curative. I don’t think I’ve ever seen a trial in lung cancer that looked at the ability of any given treatment to cure patients. We need to come up with ways to design trials to do that. Now, in addition to clinical trials, we don’t have a good body of evidence to design our preclinical experiments to look for those treatments that can lead to cures, or total eradication of cancer in whatever model system might be used. If we make cure the goal, then we need to find ways preclinically to identify those strategies that could lead to that.

Also in the realm of clinical trials, we need a very clear statistical underpinning to show that one or another treatment has a better chance of cure and to show with scientific rigor that one treatment is better than the other when it comes to cure. I think there needs to be more attention to this, and as we think about revamping the clinical trial process, we need to focus more on cure.

I’m saving the most important step for last. None of this can happen unless we try to make it happen and we say cure is possible. My mentor, George Boswell, always taught us that we would, in every single patient with cancer, try to develop a curative strategy. Is there a curative strategy for this patient? If so, pursue it with all the tools and vigor that we have. We really need to think that way.

Obviously, not every patient with cancer can be cured with our current armamentarium of anticancer treatments, but we need to make sure we put it on the table. We need to [confirm] that a strategy does not currently exist that could lead to cure. And of course, if we do find that strategy, we need to pursue it with all the energy and resources that we have.

Please don’t be afraid to use the word “cure.” Our patients want that. They deserve it. We should work hard to try to provide it and work toward developing strategies that we can propose and cure more patients.

Mark G. Kris, MD, is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York. His research interests include targeted therapies for lung cancer, multimodality therapy, the development of new anticancer drugs, and symptom management with a focus on preventing emesis.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

Hello. It’s Mark Kris from Memorial Sloan-Kettering, still musing on things I learned at ASCO 2023.

I learned that there is a new C word.

People used to be afraid to use the word “cancer,” so they would call it the C word. Hopefully we’ve gotten over that stigma, that cancer is an illness that can be fought like any other illness.

There’s a new C word now that people seem, again, afraid to use, and that word is “cure.” It’s almost a true rarity that – again, I’m talking about the lung cancer world in particular – folks use the word “cure.” I didn’t hear it at ASCO, but the truth of the matter is that’s a word we should be using and be using more.

What do our patients want? I think if you truly ask a patient what their goal of care should be, it would be to cure the illness. What I mean by “cure” is to eradicate the cancer that is in their body, keep the cancer and its effects from interfering with their ability to continue their lives, and to do it for the length of their natural life. That’s what our patients want. Yes, overall survival is important, but not as much as a life free of cancer and the burden that it puts on people having cancer in the body.

When you start thinking about cure and how to make it a goal of care, a number of issues immediately crop up. The first one is defining what is meant by “cure.” We don’t have a strict definition of cure. Again, I would probably go to the patients and ask them what they mean by it. There may be some landmark part of the definition that needs to be discussed and addressed, but again, to me it’s having your life not disturbed by cancer, and that generally comes by eradicating cancer. Living with cancer is harder than the living after cancer has been cured. But we don’t have a good definition.

We also don’t have a good way of designing clinical trials to assess whether the regimen is curative. I don’t think I’ve ever seen a trial in lung cancer that looked at the ability of any given treatment to cure patients. We need to come up with ways to design trials to do that. Now, in addition to clinical trials, we don’t have a good body of evidence to design our preclinical experiments to look for those treatments that can lead to cures, or total eradication of cancer in whatever model system might be used. If we make cure the goal, then we need to find ways preclinically to identify those strategies that could lead to that.

Also in the realm of clinical trials, we need a very clear statistical underpinning to show that one or another treatment has a better chance of cure and to show with scientific rigor that one treatment is better than the other when it comes to cure. I think there needs to be more attention to this, and as we think about revamping the clinical trial process, we need to focus more on cure.

I’m saving the most important step for last. None of this can happen unless we try to make it happen and we say cure is possible. My mentor, George Boswell, always taught us that we would, in every single patient with cancer, try to develop a curative strategy. Is there a curative strategy for this patient? If so, pursue it with all the tools and vigor that we have. We really need to think that way.

Obviously, not every patient with cancer can be cured with our current armamentarium of anticancer treatments, but we need to make sure we put it on the table. We need to [confirm] that a strategy does not currently exist that could lead to cure. And of course, if we do find that strategy, we need to pursue it with all the energy and resources that we have.

Please don’t be afraid to use the word “cure.” Our patients want that. They deserve it. We should work hard to try to provide it and work toward developing strategies that we can propose and cure more patients.

Mark G. Kris, MD, is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York. His research interests include targeted therapies for lung cancer, multimodality therapy, the development of new anticancer drugs, and symptom management with a focus on preventing emesis.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

Hello. It’s Mark Kris from Memorial Sloan-Kettering, still musing on things I learned at ASCO 2023.

I learned that there is a new C word.

People used to be afraid to use the word “cancer,” so they would call it the C word. Hopefully we’ve gotten over that stigma, that cancer is an illness that can be fought like any other illness.

There’s a new C word now that people seem, again, afraid to use, and that word is “cure.” It’s almost a true rarity that – again, I’m talking about the lung cancer world in particular – folks use the word “cure.” I didn’t hear it at ASCO, but the truth of the matter is that’s a word we should be using and be using more.

What do our patients want? I think if you truly ask a patient what their goal of care should be, it would be to cure the illness. What I mean by “cure” is to eradicate the cancer that is in their body, keep the cancer and its effects from interfering with their ability to continue their lives, and to do it for the length of their natural life. That’s what our patients want. Yes, overall survival is important, but not as much as a life free of cancer and the burden that it puts on people having cancer in the body.

When you start thinking about cure and how to make it a goal of care, a number of issues immediately crop up. The first one is defining what is meant by “cure.” We don’t have a strict definition of cure. Again, I would probably go to the patients and ask them what they mean by it. There may be some landmark part of the definition that needs to be discussed and addressed, but again, to me it’s having your life not disturbed by cancer, and that generally comes by eradicating cancer. Living with cancer is harder than the living after cancer has been cured. But we don’t have a good definition.

We also don’t have a good way of designing clinical trials to assess whether the regimen is curative. I don’t think I’ve ever seen a trial in lung cancer that looked at the ability of any given treatment to cure patients. We need to come up with ways to design trials to do that. Now, in addition to clinical trials, we don’t have a good body of evidence to design our preclinical experiments to look for those treatments that can lead to cures, or total eradication of cancer in whatever model system might be used. If we make cure the goal, then we need to find ways preclinically to identify those strategies that could lead to that.

Also in the realm of clinical trials, we need a very clear statistical underpinning to show that one or another treatment has a better chance of cure and to show with scientific rigor that one treatment is better than the other when it comes to cure. I think there needs to be more attention to this, and as we think about revamping the clinical trial process, we need to focus more on cure.

I’m saving the most important step for last. None of this can happen unless we try to make it happen and we say cure is possible. My mentor, George Boswell, always taught us that we would, in every single patient with cancer, try to develop a curative strategy. Is there a curative strategy for this patient? If so, pursue it with all the tools and vigor that we have. We really need to think that way.

Obviously, not every patient with cancer can be cured with our current armamentarium of anticancer treatments, but we need to make sure we put it on the table. We need to [confirm] that a strategy does not currently exist that could lead to cure. And of course, if we do find that strategy, we need to pursue it with all the energy and resources that we have.

Please don’t be afraid to use the word “cure.” Our patients want that. They deserve it. We should work hard to try to provide it and work toward developing strategies that we can propose and cure more patients.

Mark G. Kris, MD, is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York. His research interests include targeted therapies for lung cancer, multimodality therapy, the development of new anticancer drugs, and symptom management with a focus on preventing emesis.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

I’m Mark Kris from Memorial Sloan Kettering, discussing a recent meeting of practitioners of thoracic oncology in the metropolitan New York City area. I’ll focus on some important topics related to decision-making and daily practice, and the practitioners’ thoughts from the meeting.

There’s no doubt that our outcomes are better for patients, but it’s much harder to make the best choice and I think there’s more pressure on us to make the best choice.

Topic one was the need for next-generation sequencing (NGS) testing. I’ll put it before you that every patient needs NGS testing at the time of diagnosis. It really shouldn’t be put off. How to do that is a topic for another day, but you need NGS testing.

Moving along with this, even when you’re thinking you’re going to go down the road of a checkpoint inhibitor with chemotherapy, the recent Food and Drug Administration approval for cemiplimab and chemotherapy says that you have to make sure that patients don’t have EGFR or ALK aberrations. Now, for cemiplimab, you have to make sure they don’t have ROS1 aberrations.

You need NGS testing to find those targets and give patients a targeted therapy. Even if you want to give a checkpoint inhibitor with or without chemotherapy, you need to have NGS testing.

Second, the way to get the most comprehensive analysis of targets for which there are therapeutic avenues is to do more comprehensive NGS testing, including both DNA and RNA. Not all the panels do this right now, and you really need that RNA-based testing to find all the fusions that are druggable by the current medications that we have.

Bottom line: NGS testing should be done for everybody, and you need to do the most comprehensive panel available both for DNA and RNA.

The next topic that there was great agreement on was the emergence of antibody-drug conjugates. I think everybody’s excited. All of them have shown evidence of benefit. There are varying degrees of side effects, and we’ll learn how to deal with those. They’re new drugs, they’re here, and they’re safe.

There are a couple of things to consider, though. Number one, these drugs do have chemotherapy and they have side effects from chemotherapy. I think the consensus is that when you treat patients with an antibody-drug conjugate, you need to give antiemetic regimens, at least for trastuzumab and the other deruxtecan drugs. You need to give a regimen for highly emetogenic chemotherapy as prophylactic antiemetics. I think that was a consensus thought.

Second, these drugs are making us rethink what it means to have the expression of the protein. I’m totally struck that for trastuzumab deruxtecan, patritumab deruxtecan, and datopotamab deruxtecan, the degree of protein expression is not particularly relevant, and these drugs can work in all patients. There have been cases clearly shown that datopotamab deruxtecan and patritumab deruxtecan both have benefit in patients with EGFR mutations after progression on osimertinib.

This idea of a need for overexpression, and maybe even the idea of testing, is being challenged now. These drugs seem to work as long as some protein is present. They don’t work in every patient, but they work in the vast majority. This thinking about overexpression with the antibody-drug conjugates is probably going to need to be reevaluated.

Last are some thoughts about our targeted therapies. Again, we have more targets. We have EGFR exon 20, for example, and more drugs for MET. I’d like to share a couple of thoughts on what the experts presented at the meeting.

First, although we have a bunch of new targeted agents for patients with EGFR-mutant cancers, probably the thing that’s going to change therapy now is adding chemotherapy to these agents. We may also use circulating tumor (ctDNA) to help guide us to identify which patients would be more likely to benefit from a chemotherapy with osimertinib. I see that as a trend and as a strategy that we’re likely to see move forward.

Another is in the ALK space. I know we’ve gotten very comfortable giving alectinib and brigatinib, but when you look at all the data, it points to lorlatinib perhaps being a better first-line therapy.

I think the experts thought lorlatinib would be a good drug. Yes, it has a different spectrum of side effects. The central nervous system (CNS) side effects are something we have to learn how to take care of; however, we can do that. Generally, with dose reduction, those side effects are manageable.

If you can get better outcomes in general and in patients with brain metastases, it may make some sense to displace our go-to first-line drugs, brigatinib and alectinib, with lorlatinib.

Changes in practice are happening now. There are drugs available. I urge oncologists to be open to rethinking what your standard of care is and also open to rethinking how these drugs work and to go with the data that we have.

We’re doing much better now, but the best is yet to come.
 

Mark G. Kris, MD, is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York City. His research interests include targeted therapies for lung cancer, multimodality therapy, the development of new anticancer drugs, and symptom management with a focus on preventing emesis. A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

I’m Mark Kris from Memorial Sloan Kettering, discussing a recent meeting of practitioners of thoracic oncology in the metropolitan New York City area. I’ll focus on some important topics related to decision-making and daily practice, and the practitioners’ thoughts from the meeting.

There’s no doubt that our outcomes are better for patients, but it’s much harder to make the best choice and I think there’s more pressure on us to make the best choice.

Topic one was the need for next-generation sequencing (NGS) testing. I’ll put it before you that every patient needs NGS testing at the time of diagnosis. It really shouldn’t be put off. How to do that is a topic for another day, but you need NGS testing.

Moving along with this, even when you’re thinking you’re going to go down the road of a checkpoint inhibitor with chemotherapy, the recent Food and Drug Administration approval for cemiplimab and chemotherapy says that you have to make sure that patients don’t have EGFR or ALK aberrations. Now, for cemiplimab, you have to make sure they don’t have ROS1 aberrations.

You need NGS testing to find those targets and give patients a targeted therapy. Even if you want to give a checkpoint inhibitor with or without chemotherapy, you need to have NGS testing.

Second, the way to get the most comprehensive analysis of targets for which there are therapeutic avenues is to do more comprehensive NGS testing, including both DNA and RNA. Not all the panels do this right now, and you really need that RNA-based testing to find all the fusions that are druggable by the current medications that we have.

Bottom line: NGS testing should be done for everybody, and you need to do the most comprehensive panel available both for DNA and RNA.

The next topic that there was great agreement on was the emergence of antibody-drug conjugates. I think everybody’s excited. All of them have shown evidence of benefit. There are varying degrees of side effects, and we’ll learn how to deal with those. They’re new drugs, they’re here, and they’re safe.

There are a couple of things to consider, though. Number one, these drugs do have chemotherapy and they have side effects from chemotherapy. I think the consensus is that when you treat patients with an antibody-drug conjugate, you need to give antiemetic regimens, at least for trastuzumab and the other deruxtecan drugs. You need to give a regimen for highly emetogenic chemotherapy as prophylactic antiemetics. I think that was a consensus thought.

Second, these drugs are making us rethink what it means to have the expression of the protein. I’m totally struck that for trastuzumab deruxtecan, patritumab deruxtecan, and datopotamab deruxtecan, the degree of protein expression is not particularly relevant, and these drugs can work in all patients. There have been cases clearly shown that datopotamab deruxtecan and patritumab deruxtecan both have benefit in patients with EGFR mutations after progression on osimertinib.

This idea of a need for overexpression, and maybe even the idea of testing, is being challenged now. These drugs seem to work as long as some protein is present. They don’t work in every patient, but they work in the vast majority. This thinking about overexpression with the antibody-drug conjugates is probably going to need to be reevaluated.

Last are some thoughts about our targeted therapies. Again, we have more targets. We have EGFR exon 20, for example, and more drugs for MET. I’d like to share a couple of thoughts on what the experts presented at the meeting.

First, although we have a bunch of new targeted agents for patients with EGFR-mutant cancers, probably the thing that’s going to change therapy now is adding chemotherapy to these agents. We may also use circulating tumor (ctDNA) to help guide us to identify which patients would be more likely to benefit from a chemotherapy with osimertinib. I see that as a trend and as a strategy that we’re likely to see move forward.

Another is in the ALK space. I know we’ve gotten very comfortable giving alectinib and brigatinib, but when you look at all the data, it points to lorlatinib perhaps being a better first-line therapy.

I think the experts thought lorlatinib would be a good drug. Yes, it has a different spectrum of side effects. The central nervous system (CNS) side effects are something we have to learn how to take care of; however, we can do that. Generally, with dose reduction, those side effects are manageable.

If you can get better outcomes in general and in patients with brain metastases, it may make some sense to displace our go-to first-line drugs, brigatinib and alectinib, with lorlatinib.

Changes in practice are happening now. There are drugs available. I urge oncologists to be open to rethinking what your standard of care is and also open to rethinking how these drugs work and to go with the data that we have.

We’re doing much better now, but the best is yet to come.
 

Mark G. Kris, MD, is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York City. His research interests include targeted therapies for lung cancer, multimodality therapy, the development of new anticancer drugs, and symptom management with a focus on preventing emesis. A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

I’m Mark Kris from Memorial Sloan Kettering, discussing a recent meeting of practitioners of thoracic oncology in the metropolitan New York City area. I’ll focus on some important topics related to decision-making and daily practice, and the practitioners’ thoughts from the meeting.

There’s no doubt that our outcomes are better for patients, but it’s much harder to make the best choice and I think there’s more pressure on us to make the best choice.

Topic one was the need for next-generation sequencing (NGS) testing. I’ll put it before you that every patient needs NGS testing at the time of diagnosis. It really shouldn’t be put off. How to do that is a topic for another day, but you need NGS testing.

Moving along with this, even when you’re thinking you’re going to go down the road of a checkpoint inhibitor with chemotherapy, the recent Food and Drug Administration approval for cemiplimab and chemotherapy says that you have to make sure that patients don’t have EGFR or ALK aberrations. Now, for cemiplimab, you have to make sure they don’t have ROS1 aberrations.

You need NGS testing to find those targets and give patients a targeted therapy. Even if you want to give a checkpoint inhibitor with or without chemotherapy, you need to have NGS testing.

Second, the way to get the most comprehensive analysis of targets for which there are therapeutic avenues is to do more comprehensive NGS testing, including both DNA and RNA. Not all the panels do this right now, and you really need that RNA-based testing to find all the fusions that are druggable by the current medications that we have.

Bottom line: NGS testing should be done for everybody, and you need to do the most comprehensive panel available both for DNA and RNA.

The next topic that there was great agreement on was the emergence of antibody-drug conjugates. I think everybody’s excited. All of them have shown evidence of benefit. There are varying degrees of side effects, and we’ll learn how to deal with those. They’re new drugs, they’re here, and they’re safe.

There are a couple of things to consider, though. Number one, these drugs do have chemotherapy and they have side effects from chemotherapy. I think the consensus is that when you treat patients with an antibody-drug conjugate, you need to give antiemetic regimens, at least for trastuzumab and the other deruxtecan drugs. You need to give a regimen for highly emetogenic chemotherapy as prophylactic antiemetics. I think that was a consensus thought.

Second, these drugs are making us rethink what it means to have the expression of the protein. I’m totally struck that for trastuzumab deruxtecan, patritumab deruxtecan, and datopotamab deruxtecan, the degree of protein expression is not particularly relevant, and these drugs can work in all patients. There have been cases clearly shown that datopotamab deruxtecan and patritumab deruxtecan both have benefit in patients with EGFR mutations after progression on osimertinib.

This idea of a need for overexpression, and maybe even the idea of testing, is being challenged now. These drugs seem to work as long as some protein is present. They don’t work in every patient, but they work in the vast majority. This thinking about overexpression with the antibody-drug conjugates is probably going to need to be reevaluated.

Last are some thoughts about our targeted therapies. Again, we have more targets. We have EGFR exon 20, for example, and more drugs for MET. I’d like to share a couple of thoughts on what the experts presented at the meeting.

First, although we have a bunch of new targeted agents for patients with EGFR-mutant cancers, probably the thing that’s going to change therapy now is adding chemotherapy to these agents. We may also use circulating tumor (ctDNA) to help guide us to identify which patients would be more likely to benefit from a chemotherapy with osimertinib. I see that as a trend and as a strategy that we’re likely to see move forward.

Another is in the ALK space. I know we’ve gotten very comfortable giving alectinib and brigatinib, but when you look at all the data, it points to lorlatinib perhaps being a better first-line therapy.

I think the experts thought lorlatinib would be a good drug. Yes, it has a different spectrum of side effects. The central nervous system (CNS) side effects are something we have to learn how to take care of; however, we can do that. Generally, with dose reduction, those side effects are manageable.

If you can get better outcomes in general and in patients with brain metastases, it may make some sense to displace our go-to first-line drugs, brigatinib and alectinib, with lorlatinib.

Changes in practice are happening now. There are drugs available. I urge oncologists to be open to rethinking what your standard of care is and also open to rethinking how these drugs work and to go with the data that we have.

We’re doing much better now, but the best is yet to come.
 

Mark G. Kris, MD, is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York City. His research interests include targeted therapies for lung cancer, multimodality therapy, the development of new anticancer drugs, and symptom management with a focus on preventing emesis. A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

I’m Mark Kris from Memorial Sloan Kettering, speaking today about a topic that’s become quite controversial, which is the use of postoperative radiation therapy (PORT) in patients who have complete resections of lung cancers and who show evidence of spread to mediastinal lymph nodes, so-called N2 disease.

Data from clinical trials and data from a SEER study showed approximately 7% improvement in overall survival in patients with N2 disease who received PORT. There has been a very clear demonstration of an improved local control rate in every trial that’s ever looked at PORT.

However, there was a randomized trial, the Lung ART trial, where patients were randomized to get PORT or not. PORT was delivered in a way that is not routinely used now. In that trial, the benefit of PORT was found in terms of local control, almost doubling control within the mediastinum.

The difference in overall survival was less than 12%. Again, I’m not surprised to see that because the improvement in overall survival is probably somewhere between 5% and 10%. They also found an excess of deaths, probably due to cardiac causes from the radiation in the radiation arm.

However, the trial used a type of radiation not used at this point – it used conformal, but now we would use 3D. And its ability at the time of the trial to estimate and lower cardiac risk was not what it is today. Owing to the design of the trial, it was not a significant difference and has largely been interpreted as saying that the PORT doesn’t work.

First, let’s please go to the guidelines. I’m going to the ASCO guidelines, which say that patients with mediastinal disease should not routinely get PORT, but they should be routinely referred to a radiation oncologist for consideration of PORT. I don’t think anything that’s been published so far changes that.

I think each case needs to be individualized and requires the specialty care of a radiation oncologist to weigh the pros and cons of PORT. It also depends upon the treatment plan. Can the heart be spared? Are there radiation techniques available that would eliminate or lessen heart exposure, such as using protons? The point is that PORT is still needed.

When we look at the trials of patients receiving adjuvant therapy – and I’m looking particularly at the ADAURA trial where patients received adjuvant osimertinib – the greatest number of failures now is in the chest. We have to look for good ways to cut down on failure in the chest. Unfortunately, failure in the chest means ultimately failure and lack of cure, and we have to do a better job at that. I think PORT can play a role there.

Please, when you have patients with N2 disease, after the completion of systemic therapies, think about the use of PORT and get the advice of a radiation oncologist to meet with the patient, review their clinical situation, and assess whether or not PORT could be useful for that patient.

That is following the NCCN guidelines, which were not changed on the basis of the Lung ART paper. I think we owe it to our patients to make sure that those who could benefit from this additional therapy receive it.

I’ll put it to you that radiation delivered in the most innovative way – taking very careful account of the effects on the heart – can improve local control. There’s no question about that. I think PORT has the ability to improve survival by a small amount – probably less than 12%, which I will agree the Lung ART trial showed – but still an important amount for patients with this condition.

Mark G. Kris, MD, is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York City. He reported conflicts of interest with Arial Pharmaceuticals, Pfizer, PUMA, and Roche/Genentech. A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

I’m Mark Kris from Memorial Sloan Kettering, speaking today about a topic that’s become quite controversial, which is the use of postoperative radiation therapy (PORT) in patients who have complete resections of lung cancers and who show evidence of spread to mediastinal lymph nodes, so-called N2 disease.

Data from clinical trials and data from a SEER study showed approximately 7% improvement in overall survival in patients with N2 disease who received PORT. There has been a very clear demonstration of an improved local control rate in every trial that’s ever looked at PORT.

However, there was a randomized trial, the Lung ART trial, where patients were randomized to get PORT or not. PORT was delivered in a way that is not routinely used now. In that trial, the benefit of PORT was found in terms of local control, almost doubling control within the mediastinum.

The difference in overall survival was less than 12%. Again, I’m not surprised to see that because the improvement in overall survival is probably somewhere between 5% and 10%. They also found an excess of deaths, probably due to cardiac causes from the radiation in the radiation arm.

However, the trial used a type of radiation not used at this point – it used conformal, but now we would use 3D. And its ability at the time of the trial to estimate and lower cardiac risk was not what it is today. Owing to the design of the trial, it was not a significant difference and has largely been interpreted as saying that the PORT doesn’t work.

First, let’s please go to the guidelines. I’m going to the ASCO guidelines, which say that patients with mediastinal disease should not routinely get PORT, but they should be routinely referred to a radiation oncologist for consideration of PORT. I don’t think anything that’s been published so far changes that.

I think each case needs to be individualized and requires the specialty care of a radiation oncologist to weigh the pros and cons of PORT. It also depends upon the treatment plan. Can the heart be spared? Are there radiation techniques available that would eliminate or lessen heart exposure, such as using protons? The point is that PORT is still needed.

When we look at the trials of patients receiving adjuvant therapy – and I’m looking particularly at the ADAURA trial where patients received adjuvant osimertinib – the greatest number of failures now is in the chest. We have to look for good ways to cut down on failure in the chest. Unfortunately, failure in the chest means ultimately failure and lack of cure, and we have to do a better job at that. I think PORT can play a role there.

Please, when you have patients with N2 disease, after the completion of systemic therapies, think about the use of PORT and get the advice of a radiation oncologist to meet with the patient, review their clinical situation, and assess whether or not PORT could be useful for that patient.

That is following the NCCN guidelines, which were not changed on the basis of the Lung ART paper. I think we owe it to our patients to make sure that those who could benefit from this additional therapy receive it.

I’ll put it to you that radiation delivered in the most innovative way – taking very careful account of the effects on the heart – can improve local control. There’s no question about that. I think PORT has the ability to improve survival by a small amount – probably less than 12%, which I will agree the Lung ART trial showed – but still an important amount for patients with this condition.

Mark G. Kris, MD, is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York City. He reported conflicts of interest with Arial Pharmaceuticals, Pfizer, PUMA, and Roche/Genentech. A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

I’m Mark Kris from Memorial Sloan Kettering, speaking today about a topic that’s become quite controversial, which is the use of postoperative radiation therapy (PORT) in patients who have complete resections of lung cancers and who show evidence of spread to mediastinal lymph nodes, so-called N2 disease.

Data from clinical trials and data from a SEER study showed approximately 7% improvement in overall survival in patients with N2 disease who received PORT. There has been a very clear demonstration of an improved local control rate in every trial that’s ever looked at PORT.

However, there was a randomized trial, the Lung ART trial, where patients were randomized to get PORT or not. PORT was delivered in a way that is not routinely used now. In that trial, the benefit of PORT was found in terms of local control, almost doubling control within the mediastinum.

The difference in overall survival was less than 12%. Again, I’m not surprised to see that because the improvement in overall survival is probably somewhere between 5% and 10%. They also found an excess of deaths, probably due to cardiac causes from the radiation in the radiation arm.

However, the trial used a type of radiation not used at this point – it used conformal, but now we would use 3D. And its ability at the time of the trial to estimate and lower cardiac risk was not what it is today. Owing to the design of the trial, it was not a significant difference and has largely been interpreted as saying that the PORT doesn’t work.

First, let’s please go to the guidelines. I’m going to the ASCO guidelines, which say that patients with mediastinal disease should not routinely get PORT, but they should be routinely referred to a radiation oncologist for consideration of PORT. I don’t think anything that’s been published so far changes that.

I think each case needs to be individualized and requires the specialty care of a radiation oncologist to weigh the pros and cons of PORT. It also depends upon the treatment plan. Can the heart be spared? Are there radiation techniques available that would eliminate or lessen heart exposure, such as using protons? The point is that PORT is still needed.

When we look at the trials of patients receiving adjuvant therapy – and I’m looking particularly at the ADAURA trial where patients received adjuvant osimertinib – the greatest number of failures now is in the chest. We have to look for good ways to cut down on failure in the chest. Unfortunately, failure in the chest means ultimately failure and lack of cure, and we have to do a better job at that. I think PORT can play a role there.

Please, when you have patients with N2 disease, after the completion of systemic therapies, think about the use of PORT and get the advice of a radiation oncologist to meet with the patient, review their clinical situation, and assess whether or not PORT could be useful for that patient.

That is following the NCCN guidelines, which were not changed on the basis of the Lung ART paper. I think we owe it to our patients to make sure that those who could benefit from this additional therapy receive it.

I’ll put it to you that radiation delivered in the most innovative way – taking very careful account of the effects on the heart – can improve local control. There’s no question about that. I think PORT has the ability to improve survival by a small amount – probably less than 12%, which I will agree the Lung ART trial showed – but still an important amount for patients with this condition.

Mark G. Kris, MD, is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York City. He reported conflicts of interest with Arial Pharmaceuticals, Pfizer, PUMA, and Roche/Genentech. A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity. A version of this article first appeared on Medscape.com.

Hello. This is Mark Kris from Memorial Sloan Kettering, talking today about circulating tumor DNA (ctDNA), an emerging technology for use in perioperative patients. Recently, there have been a number of presentations about the use of ctDNA measurements in patients receiving pre- or postoperative therapies. These are critical therapies because they are given with the intention of improving the chance for cure.

All three of the presentations I’m going to mention have one thing in common: They used the so-called tumor-informed panel. The investigators took the patients’ tumor tissue, looked for cancer-related genes in that tumor tissue, and then looked for those same genes in the patient’s blood. That technology is going to become very important, as shown in these presentations.

I made one of these presentations at the European Society for Medical Oncology Immuno-Oncology virtual meeting in Geneva. In our study, we were able to find genes in the majority of patients who had tumor tissue available. These patients were preoperative surgical candidates. In 72% of these, we were able to find and track ctDNA. When we tracked the DNA in the blood, we saw that the falling levels of DNA were associated with shrinkages of the cancer radiographically – the degree of shrinkage seen in this case in the neoadjuvant examination at the time of surgery and examining the resection specimen after neoadjuvant therapy. Ultimately, the major pathologic responses were associated with clearing or falling DNA as well. Perhaps the most interesting observation is that when you put this DNA information together with the major pathologic response information, all of the patients who had clearance of ctDNA and had a major pathologic response were disease free. I believe that eventually we will use this ctDNA data in conjunction with other measures of benefit to reach a more precise assessment of therapy benefit, and eventually it may be helpful for prognosis as well.

Two other studies also used this technology. One was earlier this year, presented by Patrick Forde at the American Association for Cancer Research meeting. They associated changes in ctDNA using another tumor-informed assay. In that study, using the Archer assay, they were able to show that the ctDNA clearance was associated with a complete pathologic response. So again, combining this information provides a more precise measurement of the benefit of therapy.

Another presentation at ESMO Immuno-Oncology, by Caicun Zhou, looked at the Natera assay, another tumor-informed assay, in a trial of adjuvant atezolizumab. This group showed that patients who had clearance of their ctDNA after surgery had the greatest benefit from subsequent atezolizumab therapy. And even those patients who did not have clearance experienced some benefit of the atezolizumab therapy. In addition, they assessed the degree of benefit associated with whether or not PD-L1 was present. Those patients who had PD-L1 expression experienced the greatest benefit from the atezolizumab. For patients who didn’t have PD-L1 expression, where you wouldn’t expect atezolizumab to have this greater benefit, they didn’t see it.

I believe that ctDNA-informed testing will become more and more useful, both in clinical trials and ultimately in the care of patients with early-stage lung cancers. These tumor-informed assays are going to be standards of care and provide physicians and patients a better estimate of the effectiveness of therapy going forward.

Dr. Kris is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York. He reported serving as a consultant and/or adviser for AstraZeneca, Daiichi Sankyo, and Pfizer, and has received payments for various services from Genentech.

This transcript has been edited for clarity. A version of this article first appeared on Medscape.com.

Hello. This is Mark Kris from Memorial Sloan Kettering, talking today about circulating tumor DNA (ctDNA), an emerging technology for use in perioperative patients. Recently, there have been a number of presentations about the use of ctDNA measurements in patients receiving pre- or postoperative therapies. These are critical therapies because they are given with the intention of improving the chance for cure.

All three of the presentations I’m going to mention have one thing in common: They used the so-called tumor-informed panel. The investigators took the patients’ tumor tissue, looked for cancer-related genes in that tumor tissue, and then looked for those same genes in the patient’s blood. That technology is going to become very important, as shown in these presentations.

I made one of these presentations at the European Society for Medical Oncology Immuno-Oncology virtual meeting in Geneva. In our study, we were able to find genes in the majority of patients who had tumor tissue available. These patients were preoperative surgical candidates. In 72% of these, we were able to find and track ctDNA. When we tracked the DNA in the blood, we saw that the falling levels of DNA were associated with shrinkages of the cancer radiographically – the degree of shrinkage seen in this case in the neoadjuvant examination at the time of surgery and examining the resection specimen after neoadjuvant therapy. Ultimately, the major pathologic responses were associated with clearing or falling DNA as well. Perhaps the most interesting observation is that when you put this DNA information together with the major pathologic response information, all of the patients who had clearance of ctDNA and had a major pathologic response were disease free. I believe that eventually we will use this ctDNA data in conjunction with other measures of benefit to reach a more precise assessment of therapy benefit, and eventually it may be helpful for prognosis as well.

Two other studies also used this technology. One was earlier this year, presented by Patrick Forde at the American Association for Cancer Research meeting. They associated changes in ctDNA using another tumor-informed assay. In that study, using the Archer assay, they were able to show that the ctDNA clearance was associated with a complete pathologic response. So again, combining this information provides a more precise measurement of the benefit of therapy.

Another presentation at ESMO Immuno-Oncology, by Caicun Zhou, looked at the Natera assay, another tumor-informed assay, in a trial of adjuvant atezolizumab. This group showed that patients who had clearance of their ctDNA after surgery had the greatest benefit from subsequent atezolizumab therapy. And even those patients who did not have clearance experienced some benefit of the atezolizumab therapy. In addition, they assessed the degree of benefit associated with whether or not PD-L1 was present. Those patients who had PD-L1 expression experienced the greatest benefit from the atezolizumab. For patients who didn’t have PD-L1 expression, where you wouldn’t expect atezolizumab to have this greater benefit, they didn’t see it.

I believe that ctDNA-informed testing will become more and more useful, both in clinical trials and ultimately in the care of patients with early-stage lung cancers. These tumor-informed assays are going to be standards of care and provide physicians and patients a better estimate of the effectiveness of therapy going forward.

Dr. Kris is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York. He reported serving as a consultant and/or adviser for AstraZeneca, Daiichi Sankyo, and Pfizer, and has received payments for various services from Genentech.

This transcript has been edited for clarity. A version of this article first appeared on Medscape.com.

Hello. This is Mark Kris from Memorial Sloan Kettering, talking today about circulating tumor DNA (ctDNA), an emerging technology for use in perioperative patients. Recently, there have been a number of presentations about the use of ctDNA measurements in patients receiving pre- or postoperative therapies. These are critical therapies because they are given with the intention of improving the chance for cure.

All three of the presentations I’m going to mention have one thing in common: They used the so-called tumor-informed panel. The investigators took the patients’ tumor tissue, looked for cancer-related genes in that tumor tissue, and then looked for those same genes in the patient’s blood. That technology is going to become very important, as shown in these presentations.

I made one of these presentations at the European Society for Medical Oncology Immuno-Oncology virtual meeting in Geneva. In our study, we were able to find genes in the majority of patients who had tumor tissue available. These patients were preoperative surgical candidates. In 72% of these, we were able to find and track ctDNA. When we tracked the DNA in the blood, we saw that the falling levels of DNA were associated with shrinkages of the cancer radiographically – the degree of shrinkage seen in this case in the neoadjuvant examination at the time of surgery and examining the resection specimen after neoadjuvant therapy. Ultimately, the major pathologic responses were associated with clearing or falling DNA as well. Perhaps the most interesting observation is that when you put this DNA information together with the major pathologic response information, all of the patients who had clearance of ctDNA and had a major pathologic response were disease free. I believe that eventually we will use this ctDNA data in conjunction with other measures of benefit to reach a more precise assessment of therapy benefit, and eventually it may be helpful for prognosis as well.

Two other studies also used this technology. One was earlier this year, presented by Patrick Forde at the American Association for Cancer Research meeting. They associated changes in ctDNA using another tumor-informed assay. In that study, using the Archer assay, they were able to show that the ctDNA clearance was associated with a complete pathologic response. So again, combining this information provides a more precise measurement of the benefit of therapy.

Another presentation at ESMO Immuno-Oncology, by Caicun Zhou, looked at the Natera assay, another tumor-informed assay, in a trial of adjuvant atezolizumab. This group showed that patients who had clearance of their ctDNA after surgery had the greatest benefit from subsequent atezolizumab therapy. And even those patients who did not have clearance experienced some benefit of the atezolizumab therapy. In addition, they assessed the degree of benefit associated with whether or not PD-L1 was present. Those patients who had PD-L1 expression experienced the greatest benefit from the atezolizumab. For patients who didn’t have PD-L1 expression, where you wouldn’t expect atezolizumab to have this greater benefit, they didn’t see it.

I believe that ctDNA-informed testing will become more and more useful, both in clinical trials and ultimately in the care of patients with early-stage lung cancers. These tumor-informed assays are going to be standards of care and provide physicians and patients a better estimate of the effectiveness of therapy going forward.

Dr. Kris is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York. He reported serving as a consultant and/or adviser for AstraZeneca, Daiichi Sankyo, and Pfizer, and has received payments for various services from Genentech.

This transcript has been edited for clarity. The transcript and an accompanying video first appeared on Medscape.com.

This is Mark Kris from chilly New York and Memorial Sloan Kettering. Today I want to talk about a recent article in the Journal of Clinical Oncology that reported a study of a new neurokinin-1 antagonist called fosnetupitant. This was a well-conducted trial that demonstrates the noninferiority of IV fosnetupitant when compared with IV fosaprepitant. By their study criteria, fosnetupitant was not inferior.

But my reason for discussing this is that the paper and the trial miss the point for the field right now. Although the authors talk about the prevention of nausea and vomiting in the introduction, in the paper itself and in the abstract results section, there’s not a single mention about the medication’s ability to control nausea, which is the critical issue for our patients today. You have to go into the supplementary data to find it mentioned, and what you find is that the prevention of nausea is 50% for both the control and this new drug. We control nausea in only half of the patients who receive cisplatin in 2022. That is a huge issue.

When you ask patients what are the effects of cancer treatment that they fear most, that concerns them most, it’s nausea and emesis; indeed, nausea has replaced emesis as the biggest concern. And although this trial used emesis as the main endpoint, and it was useful in defining the drug, it was not useful in coming up with a new treatment that addresses a huge need. Further, the authors talk about an advantage to fosnetupitant based on infusion reactions, but it is a difference of 0.3% vs. 3%. They talk about that sort of thing in the abstract and in the discussion section but don’t include nausea as part of the key endpoint of this trial. Again, you had to dig deeply to find out that, frankly, fosnetupitant was no better than the drugs we already have.

The other concerning point is that we do have another drug that works well. If you go to the American Society of Clinical Oncology or National Comprehensive Cancer Network guidelines for patients receiving high dosages of cisplatin, you find a four-drug regimen, including olanzapine, and that was not used here. Why is olanzapine so critical? It’s an available drug, it’s an inexpensive drug, it’s a safe drug, and it improves nausea by 15%.

So they did this huge trial to show noninferiority, and they neglected to give a drug that could deal with the most serious side effect of cancer therapy – nausea – and improve things by 15%.

A challenge to people in this field: We have to do better. Nausea is a big problem. While noninferiority trials can be helpful for drug development, they’re not really helpful for the field. With a problem of this magnitude, we need better drugs to control nausea. In the meantime, I urge you all to follow the guidelines for high doses of cisplatin. Please use the four-drug regimen that is recommended in the guidelines and widely used in the United States. Going forward, make sure that when we expend huge amounts of energy to develop new agents and report them in our medical journals, that we look for ways to advance care where there are significant gaps in our ability to deliver what we want. Delivering better control of nausea is something we all need to be committed to. It’s a huge unmet need, and I hope future trials will address that need. Our patients will be better for it and we’ll be better in that we’re delivering what patients deserve, what they need, and what they ask for.

Mark G. Kris, MD, is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York City. He reported serving as a director, officer, partner, employee, adviser, consultant, or trustee for AstraZeneca, Roche/Genentech, and Ariad Pharmaceuticals, and has received research grants from Pfizer, PUMA, and Roche/Genentech.

This transcript has been edited for clarity. The transcript and an accompanying video first appeared on Medscape.com.

This is Mark Kris from chilly New York and Memorial Sloan Kettering. Today I want to talk about a recent article in the Journal of Clinical Oncology that reported a study of a new neurokinin-1 antagonist called fosnetupitant. This was a well-conducted trial that demonstrates the noninferiority of IV fosnetupitant when compared with IV fosaprepitant. By their study criteria, fosnetupitant was not inferior.

But my reason for discussing this is that the paper and the trial miss the point for the field right now. Although the authors talk about the prevention of nausea and vomiting in the introduction, in the paper itself and in the abstract results section, there’s not a single mention about the medication’s ability to control nausea, which is the critical issue for our patients today. You have to go into the supplementary data to find it mentioned, and what you find is that the prevention of nausea is 50% for both the control and this new drug. We control nausea in only half of the patients who receive cisplatin in 2022. That is a huge issue.

When you ask patients what are the effects of cancer treatment that they fear most, that concerns them most, it’s nausea and emesis; indeed, nausea has replaced emesis as the biggest concern. And although this trial used emesis as the main endpoint, and it was useful in defining the drug, it was not useful in coming up with a new treatment that addresses a huge need. Further, the authors talk about an advantage to fosnetupitant based on infusion reactions, but it is a difference of 0.3% vs. 3%. They talk about that sort of thing in the abstract and in the discussion section but don’t include nausea as part of the key endpoint of this trial. Again, you had to dig deeply to find out that, frankly, fosnetupitant was no better than the drugs we already have.

The other concerning point is that we do have another drug that works well. If you go to the American Society of Clinical Oncology or National Comprehensive Cancer Network guidelines for patients receiving high dosages of cisplatin, you find a four-drug regimen, including olanzapine, and that was not used here. Why is olanzapine so critical? It’s an available drug, it’s an inexpensive drug, it’s a safe drug, and it improves nausea by 15%.

So they did this huge trial to show noninferiority, and they neglected to give a drug that could deal with the most serious side effect of cancer therapy – nausea – and improve things by 15%.

A challenge to people in this field: We have to do better. Nausea is a big problem. While noninferiority trials can be helpful for drug development, they’re not really helpful for the field. With a problem of this magnitude, we need better drugs to control nausea. In the meantime, I urge you all to follow the guidelines for high doses of cisplatin. Please use the four-drug regimen that is recommended in the guidelines and widely used in the United States. Going forward, make sure that when we expend huge amounts of energy to develop new agents and report them in our medical journals, that we look for ways to advance care where there are significant gaps in our ability to deliver what we want. Delivering better control of nausea is something we all need to be committed to. It’s a huge unmet need, and I hope future trials will address that need. Our patients will be better for it and we’ll be better in that we’re delivering what patients deserve, what they need, and what they ask for.

Mark G. Kris, MD, is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York City. He reported serving as a director, officer, partner, employee, adviser, consultant, or trustee for AstraZeneca, Roche/Genentech, and Ariad Pharmaceuticals, and has received research grants from Pfizer, PUMA, and Roche/Genentech.

This transcript has been edited for clarity. The transcript and an accompanying video first appeared on Medscape.com.

This is Mark Kris from chilly New York and Memorial Sloan Kettering. Today I want to talk about a recent article in the Journal of Clinical Oncology that reported a study of a new neurokinin-1 antagonist called fosnetupitant. This was a well-conducted trial that demonstrates the noninferiority of IV fosnetupitant when compared with IV fosaprepitant. By their study criteria, fosnetupitant was not inferior.

But my reason for discussing this is that the paper and the trial miss the point for the field right now. Although the authors talk about the prevention of nausea and vomiting in the introduction, in the paper itself and in the abstract results section, there’s not a single mention about the medication’s ability to control nausea, which is the critical issue for our patients today. You have to go into the supplementary data to find it mentioned, and what you find is that the prevention of nausea is 50% for both the control and this new drug. We control nausea in only half of the patients who receive cisplatin in 2022. That is a huge issue.

When you ask patients what are the effects of cancer treatment that they fear most, that concerns them most, it’s nausea and emesis; indeed, nausea has replaced emesis as the biggest concern. And although this trial used emesis as the main endpoint, and it was useful in defining the drug, it was not useful in coming up with a new treatment that addresses a huge need. Further, the authors talk about an advantage to fosnetupitant based on infusion reactions, but it is a difference of 0.3% vs. 3%. They talk about that sort of thing in the abstract and in the discussion section but don’t include nausea as part of the key endpoint of this trial. Again, you had to dig deeply to find out that, frankly, fosnetupitant was no better than the drugs we already have.

The other concerning point is that we do have another drug that works well. If you go to the American Society of Clinical Oncology or National Comprehensive Cancer Network guidelines for patients receiving high dosages of cisplatin, you find a four-drug regimen, including olanzapine, and that was not used here. Why is olanzapine so critical? It’s an available drug, it’s an inexpensive drug, it’s a safe drug, and it improves nausea by 15%.

So they did this huge trial to show noninferiority, and they neglected to give a drug that could deal with the most serious side effect of cancer therapy – nausea – and improve things by 15%.

A challenge to people in this field: We have to do better. Nausea is a big problem. While noninferiority trials can be helpful for drug development, they’re not really helpful for the field. With a problem of this magnitude, we need better drugs to control nausea. In the meantime, I urge you all to follow the guidelines for high doses of cisplatin. Please use the four-drug regimen that is recommended in the guidelines and widely used in the United States. Going forward, make sure that when we expend huge amounts of energy to develop new agents and report them in our medical journals, that we look for ways to advance care where there are significant gaps in our ability to deliver what we want. Delivering better control of nausea is something we all need to be committed to. It’s a huge unmet need, and I hope future trials will address that need. Our patients will be better for it and we’ll be better in that we’re delivering what patients deserve, what they need, and what they ask for.

Mark G. Kris, MD, is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York City. He reported serving as a director, officer, partner, employee, adviser, consultant, or trustee for AstraZeneca, Roche/Genentech, and Ariad Pharmaceuticals, and has received research grants from Pfizer, PUMA, and Roche/Genentech.

Presented during the ASCO 2020 plenary session, the results of the phase 3 ADAURA trial will prove practice-changing, according to Dr. Mark Kris of Memorial Sloan Kettering Cancer Center. Over 600 patients whose resected tumors were found to have EGFR mutations were treated with osimertinib. The results more than doubled disease-free survival rates, from 44% to 90% at 2 years.

Among other adjuvant trials, the phase 2 VISION study looked at tepotinib, a once-daily, highly selective oral MET inhibitor. The study showed durable responses coupled with acceptable side effects. The drug has been given fast-track status by the US Food and Drug Administration.

Dr. Kris notes that the DESTINY study introduces trastuzumab deruxtecan, an antibody-drug conjugate, as a promising new class of drugs for lung cancer patients. Interim results presented at ASCO further support the HER2 mutation as another potential target for patients with lung cancer.

Finally, the phase 2 CITYSCAPE study provides preliminary evidence for a new checkpoint inhibitor. The monoclonal antibody tiragolumab was developed to block TIGIT. The study showed that the combination of tiragolumab and atezolizumab can improve both rates of response and time to disease recurrence — results Dr. Kris considers encouraging for patients with advanced lung cancer.

Mark G. Kris, MD

Mark G. Kris, MD, Professor, Department of Medicine, Weill Cornell Medical College; Attending Physician, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.

Presented during the ASCO 2020 plenary session, the results of the phase 3 ADAURA trial will prove practice-changing, according to Dr. Mark Kris of Memorial Sloan Kettering Cancer Center. Over 600 patients whose resected tumors were found to have EGFR mutations were treated with osimertinib. The results more than doubled disease-free survival rates, from 44% to 90% at 2 years.

Among other adjuvant trials, the phase 2 VISION study looked at tepotinib, a once-daily, highly selective oral MET inhibitor. The study showed durable responses coupled with acceptable side effects. The drug has been given fast-track status by the US Food and Drug Administration.

Dr. Kris notes that the DESTINY study introduces trastuzumab deruxtecan, an antibody-drug conjugate, as a promising new class of drugs for lung cancer patients. Interim results presented at ASCO further support the HER2 mutation as another potential target for patients with lung cancer.

Finally, the phase 2 CITYSCAPE study provides preliminary evidence for a new checkpoint inhibitor. The monoclonal antibody tiragolumab was developed to block TIGIT. The study showed that the combination of tiragolumab and atezolizumab can improve both rates of response and time to disease recurrence — results Dr. Kris considers encouraging for patients with advanced lung cancer.

Mark G. Kris, MD

Mark G. Kris, MD, Professor, Department of Medicine, Weill Cornell Medical College; Attending Physician, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.

Presented during the ASCO 2020 plenary session, the results of the phase 3 ADAURA trial will prove practice-changing, according to Dr. Mark Kris of Memorial Sloan Kettering Cancer Center. Over 600 patients whose resected tumors were found to have EGFR mutations were treated with osimertinib. The results more than doubled disease-free survival rates, from 44% to 90% at 2 years.

Among other adjuvant trials, the phase 2 VISION study looked at tepotinib, a once-daily, highly selective oral MET inhibitor. The study showed durable responses coupled with acceptable side effects. The drug has been given fast-track status by the US Food and Drug Administration.

Dr. Kris notes that the DESTINY study introduces trastuzumab deruxtecan, an antibody-drug conjugate, as a promising new class of drugs for lung cancer patients. Interim results presented at ASCO further support the HER2 mutation as another potential target for patients with lung cancer.

Finally, the phase 2 CITYSCAPE study provides preliminary evidence for a new checkpoint inhibitor. The monoclonal antibody tiragolumab was developed to block TIGIT. The study showed that the combination of tiragolumab and atezolizumab can improve both rates of response and time to disease recurrence — results Dr. Kris considers encouraging for patients with advanced lung cancer.

Mark G. Kris, MD

Mark G. Kris, MD, Professor, Department of Medicine, Weill Cornell Medical College; Attending Physician, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.