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In a field of poor outcomes, few standards of care, and small populations of patients scattered across the world, investigators studying rare genitourinary (GU) cancers are gaining ground through international collaboration and novel trial design.
Fundamental clinical questions in the area remain unanswered, including the value of conventional treatments, such as chemotherapy and surgery, vs. emerging immunotherapy combinations.
Managing patients with rare GU cancers presents a variety of challenges, as does conducting research in the field, according to Philippe E. Spiess, MD, MS, FACS, assistant chief of surgical services and senior member in the department of GU oncology at Moffitt Cancer Center, Tampa.
“Unfortunately, there are limited resources for patients – from an education, from a patient advocacy, and ultimately also from a research standpoint,” Dr. Spiess said in an interview, noting difficulties in attaining funding and reaching meaningful endpoints.
The Global Society of Rare Genitourinary Tumors
Last year Dr. Spiess teamed up with Andrea Necchi, MD, of the department of medical oncology at Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, to found the Global Society of Rare Genitourinary Tumors (GSRGT), the first organization of its kind.
“We’ve formally established a society and gotten some of the world leaders [in the field] … to work with us in developing educational tools and patient advocacy efforts to really promote and improve the care of patients impacted with rare cancers,” Dr. Spiess said.
He went on to highlight the truly global makeup of GSRGT, which includes members from leading centers in North America, South America, Europe, and India, and described it as a “grass-roots” organization that he and Dr. Necchi privately funded without financial backing from pharmaceutical companies.
The first GSRGT summit took place in 2020; it focused on penile and testis cancers and was attended by more than 350 participants. The second summit, planned for March 2022, in a virtual format, will focus on rare kidney cancers and upper tract cancers.
“We’ll definitely be having a lot of important conversations about important unmet needs, and some of the important clinical trials that patients and clinicians should be aware of,” Dr. Spiess said.
Dr. Spiess is currently involved in the International Penile Advanced Cancer Trial(InPACT), which is aiming to enroll 200 patients with squamous cell carcinoma of the penis. The randomized study will compare outcomes across patients treated with standard surgery alone, neoadjuvant chemotherapy plus surgery, and neoadjuvant chemoradiotherapy plus surgery.
“I think this is going to be a landmark study because it’s going to give really baseline high-quality data on the effectiveness of these therapies,” Dr. Spiess said.
Results are expected in 2024.
Basket trials open doors for patients in need
Other investigators are testing immunotherapy combinations in patients with rare GU tumors via nonrandomized basket trials, which widen inclusion criteria and improve local availability.
According to Bradley McGregor, MD, clinical director of the Lank Center for GU Oncology at the Dana-Farber Cancer Institute in Boston, early results from these trials are promising, both in terms of therapeutic efficacy and the approach itself.
“Patients [with rare GU tumors] would come to us saying, ‘Well, what can we do? What trial?’,” Dr. McGregor said. “But really, there was no trial to get them on.”Basket trials are therefore needed, he said, as they accelerate progress in the field and help meet patient needs.
“For some of these relatively rare diseases … there is no standard of care,” Dr. McGregor said. “And low incidence makes it challenging to conduct a dedicated clinical trial. Those patients are left with minimal therapeutic options. … We look to provide care for that unmet need.”Andrea B. Apolo, MD, described similar experiences as head of the bladder cancer section of the GU malignancies branch of the National Cancer Institute (NCI), Bethesda, Md.
“I’ve been at the NCI for the past 10 years and I’ve gotten a lot of referrals for rare tumors,” Dr. Apolo said. “[These patients] have tried all available standard of care options, and therefore are often looking for clinical trials and new drugs – any kind of therapy that may be effective for their disease.”This call for help, along with a growing scientific curiosity, motivated Dr. Apolo to design trials that would include patients who had nowhere else to go.
“I became very interested in … understanding more about the mechanism of tumorigenesis and understanding rare tumors, biologically, within the lab,” she said, “but also clinically, in terms of finding more effective therapies.”
Both Dr. McGregor and Dr. Apolo are currently conducting basket trials for patients with rare GU tumors. While Dr. McGregor is testing a combination of PD-1 inhibitor nivolumab and CTLA-4 inhibitor ipilimumab, Dr. Apolo is exploring the benefit of cabozantinib, a targeted therapy, given with either nivolumab or nivolumab plus ipilimumab.
When asked about these trials, Dr. Spiess said that “basket trials are important because they may give us an understanding of some potentially useful therapies or combinations;” however, he also pointed out their limitations, noting that they may inaccurately characterize the efficacy of given therapies over a broad array of disease entities even if they are of similar histology. As an example, he noted “very different” genomic profiles across squamous cell carcinomas of the pelvis depending on exact anatomical location, suggesting that these differences may affect responses to therapy, citing a recent study in European Urology that he conducted with Dr. Necchi.1
“[Basket trials] are probably not going to be the be-all-end-all,” Dr. Spiess said. “It really requires a global initiative to do these types of studies, which the Global Society of Rare Genitourinary Tumors will allow.”
Exploring immunotherapy combinations
Despite the potential limitations, recent basket trials involving immunotherapy regimens have been associated with overall response rates, in some subgroups, that exceed 35%.2,3
In comparison with previous trials, many of which had response rates in the single digits, or no responses at all, these results are, in Dr. McGregor’s words, “very thought provoking.”Most rare GU malignancies fall into one of four categories: bladder cancer variant histology (BCVH), adrenal tumors, penile squamous cell carcinoma (PSCC), and chemotherapy-refractory germ cell tumors (CRGCT). Among these, BCVH has the strongest evidence supporting clinical use of immunotherapy, based on U.S. approval for urothelial histology, according to Dr. McGregor.4Data supporting immunotherapy for the remaining disease subtypes are scarce. Although pembrolizumab is approved for patients with solid tumors that exhibit microsatellite instability (MSI), MSI is uncommon among patients with rare GU cancers; estimated incidence rates are less than 10%.4
“As such, clinical trials to address this unmet need are imperative,” Dr. McGregor wrote in a recent review article.4
According to Dr. McGregor, programmed death ligand 1 (PD-L1) expression in rare GU tumors may be relatively common in some disease subtypes, such as PSCC, which has a PD-L1 expression rate of up to 60%.4
But rare GU tumor trials involving a single checkpoint inhibitor have produced limited results, if any.
The largest trial for adrenocortical carcinoma (ACC), for example, which included 50 patients, showed that avelumab resulted in an objective response rate (ORR) of just 6%.5
Pembrolizumab was slightly more effective for ACC, based on a trial involving 39 patients, which returned an ORR of 23%, and another trial involving 15 patients that had a 15% ORR.6,7
Two other trials, which tested single-agent pembrolizumab or durvalumab in patients with CRGCT, resulted in no responses at all, whereas a trial testing pembrolizumab alone for penile squamous cell carcinoma was terminated in 2020, citing poor accrual.8,9 Still, the durvalumab trial for CRGCT, led by Dr. Necchi, did offer a glimpse at what might be possible with a combination of immunotherapies. Although no responses were observed among 11 patients who received durvalumab alone, an efficacy signal was observed in a second cohort of 11 patients who were given durvalumab in combination with the CTLA-4 inhibitor tremilimumab.9
Out of those 11 patients, 1 had a partial response, and another achieved stable disease.
In light of these findings, and more that have been published since then, the clinical trial landscape for rare GU tumors is shifting toward a combination immunotherapy approach, according to Dr. McGregor.4
Nivolumab and ipilimumab
Dr. McGregor is leading a phase II trial (NCT03333616) testing a combination of nivolumab and ipilimumab in patients with a variety of advanced rare GU malignancies, including bladder and upper tract carcinoma of variant histology (BUTCVH), adrenal tumors, CRGCT, PSCC, and prostate cancer of variant histology (PCVH).
“When trials are designed, these patients are often forgotten,” Dr. McGregor noted. “We said, let’s do a trial for all rare GU tumors and just sort of assess and look for a signal, and, hopefully, find a signal that we can then take to the next level.”
Along with appropriate disease phenotype, trial eligibility depended upon an ECOG performance status of 0-2 and no prior exposure to checkpoint inhibitors. Treatment-naive patients were allowed. All participants received nivolumab 3 mg/kg and ipilimumab 1 mg/kg IV every 3 weeks for four doses, followed by maintenance nivolumab at a dose of 480 mg every 4 weeks.
Most recent results, published in Cancer, included data from 55 patients, including 19 with BUTCVH, 18 with adrenal tumors, and 18 with other tumors.3 After a median follow-up of 9.9 months, 28 patients (51%) received all four doses of the regimen, 25 of whom received maintenance therapy with a median of four cycles.
Overall, nine patients (16%) responded to therapy, six of whom (67%) maintained their response for at least 9 months. Two responses were complete, and seven were partial. Median progression-free survival was 2.8 months.
Twenty-two patients (39%) had grade 3 or higher treatment-related adverse events, approximately one-quarter (23%) needed high-dose steroids, and a slightly greater proportion (27%) discontinued the regimen because of adverse events. Three patients exhibited grade 5 toxicity, and one patient death was treatment related. A closer look at the efficacy data suggested that one disease subgroup benefited much more than the others. The overall response rate among 19 patients with BUTCVH was 37%, compared with 6% in the other two cohorts.
“A response rate of 37% compares quite favorably to anything we’ve seen to date,” Dr. McGregor said. “It’s remarkable that [this response] was seen across histologies – we saw this in urachal, we saw this in adenocarcinoma – we really saw this across the board. This is very, very, very intriguing data.”
The phase II trial is ongoing at multiple centers across the country, including the Dana-Farber/Harvard Cancer Center, Boston, the University of Texas MD Anderson Cancer Center, Houston, the Moores Cancer Center at University of California Health, San Diego, the Ohio State University Comprehensive Cancer Center, Columbus, and the Winship Cancer Institute of Emory University, Atlanta.
“We accrued this trial in just under 18 months,” Dr. McGregor said. “I think this shows that with a well-designed trial, we can actually study these diseases and improve outcomes in these patients.” According to Dr. McGregor, the current findings deserve further investigation, potentially including expansion of the BUTCVH cohort. Recruitment is ongoing for a fourth cohort involving patients with tumors that exhibit neuroendocrine differentiation.
Cabozantinib and nivolumab with or without ipilimumab
Dr. Apolo is leading a similar basket trial (NCT02496208) that is testing cabozantinib plus nivolumab with or without ipilimumab.
“What we’re doing is using immunotherapy and a targeted therapy that work in standard urothelial carcinoma and renal cell carcinoma,” Dr. Apolo said. “But really, we don’t know the activity in these rare GU tumors. … There’s still so much we don’t understand about what the driving mutations are, and how we can best target them.”
Most recent data, published in Journal of Clinical Oncology, include 122 patients with metastatic GU tumors, including urothelial carcinoma, clear cell renal cell carcinoma, bladder adenocarcinoma, and other rare GU cancers.2
Among these patients, 54 were in the phase I dose-finding cohort (eight escalating doses) and 64 were in the dose-expansion cohorts.
After a median follow-up of 40.4 months, 64 patients received the dual combination, whereas 56 received the triplet regimen. The ORR for 108 evaluable patients was 38%, including 12 complete responses (11.1%) and 29 partial responses (26.9%). The largest disease cohort, for urothelial carcinoma, included 33 patients and was associated with an ORR of 42.4%, with a complete response rate of 21.2%. Objective response rate was highest for squamous bladder cancer (85.7%; n = 7), followed by clear cell renal carcinoma (62.5%; n = 16), renal medullary cancer (50%; n = 2), penile cancer (44.4%; n = 9), small cell bladder cancer (33.1%; n = 3), bladder adenocarcinoma (20%; n = 15), and prostate cancer (11.1%; n = 9). No responses were seen in six patients with germ cell tumors.
Adding ipilimumab appeared to have a minimal impact on toxicity. Grade 3 or 4 treatment-related adverse events (AEs) occurred in 84% of patients in the dual combination group, compared with 80% receiving the triplet regimen. Most common AEs were hypophosphatemia (16-25%), lipase elevation (20%), fatigue (18-20%), ALT elevation (5-14%), AST elevation (9-11%), diarrhea (9-11%), and thromboembolic event (4-11%). One patient taking the triplet regimen had grade 5 pneumonitis.
These positive phase I results have paved the way for the phase II ICONIC trial (NCT03866382), a national study available through the Alliance Cooperative Group. The trial is currently recruiting, with an estimated enrollment of 224 patients with rare GU tumors.
The ICONIC trial is just one of several studies that Dr. Apolo is conducting for patients with rare GU cancer. “I have several bladder cancer trials where I’m accepting rare GU tumors to enroll,” she said, noting that efficacy signals in these exploratory cohorts may be pursued with expansion studies like ICONIC.
This inclusive strategy is uncovering promising new treatments for some rare GU malignancies, but the rarest of the rare tumor types remain challenging to study, Dr. Apolo said, because very small sample sizes can preclude significant data. “Although we do have the referral base at the NCI, we still get a small number of a lot of rare tumors,” Dr. Apolo said. “What I end up having, a lot of time, are small subsets of rare tumors – I’ll have 4 of one kind, 10 of another.” This situation means that sometimes, time and resources must be focused where they are needed most.
“Sometimes I actually have to decide which are the more common rare tumors so I can study them in a larger cohort,” Dr. Apolo said. “It can have more clinical impact within the community of that rare tumor.” Dr. Apolo described the inherent conflict involved in this decision, but also, its ultimate necessity.
“It’s what you don’t want to do, but you end up doing,” she said. “Because you want to be inclusive and include the rare, rare tumor, but sometimes you just can’t get enough numbers to see if there’s actually a difference [in efficacy]. If it doesn’t work in one patient, does that mean it doesn’t work at all? You need more numbers to really test the efficacy of therapy.”
From clinical trials to clinical practice
To accrue the number of patients needed for practice-altering findings, both Dr. McGregor and Dr. Apolo emphasized the importance of institutional support and collaborative trial designs.
“The FDA is a great ally,” Dr. McGregor said. “They’re acutely aware of the challenges facing patients with rare malignancies – not just GU malignancies. They’re continuing to evaluate the best way to move these drugs forward for those patients. … They’re constantly working with investigators, with industry, looking at data and trying to determine at what threshold these will be practice-changing studies.”
Dr. McGregor suggested that larger trials could shift national guideline recommendations toward combination immunotherapies for patients with rare GU tumors, which would lead to inclusion in compendia, and from there, broader clinical usage.
“At end of the day, luckily, we’re not dealing with drugs that aren’t available,” Dr. McGregor said. “These are drugs that are readily available, approved by the FDA in other settings.”
Dr. Apolo also described strong support from the NCI.
“The NCI really encourages the conduction and enrollment of these rare GU tumor trials, because they understand that the NCI is a really good place to study these rare tumors,” she said. “We have unique resources that make it feasible to conduct some of these trials.”
Dr. Apolo also praised the Alliance Cooperative Group for helping expand patient access to rare GU tumor trials.
“[The Alliance Cooperative Group] makes trials available at community centers across the country,” Dr. Apolo said. “Patients don’t have to travel to the NCI, and they can get the same therapies.”
Still, Dr. Apolo recommended that, when possible, clinicians refer patients with newly diagnosed, rare GU tumors to centers that see a higher number of such cases.
“It’s hard to keep up with all the different treatments that are available right now for different cancers,” Dr. Apolo said. “And sometimes for the rare tumors, there may be great opportunities within a clinical trial that a cancer center may have available that may not be available locally in the community.”
For patients who would like to learn more about rare bladder cancers, Dr. Apolo recommended a visit to the Bladder Cancer Advocacy Network (BCAN) website (bcan.org).
“I’m a big fan of these patient-centered advocacy networks,” Dr. Apolo said. “I like BCAN a lot. It’s a patient-run organization for patients with bladder cancer. With them, I have done a couple of webinars for rare bladder tumors that Ive had some patients tell me are very helpful. They’re a terrific organization that really provides not only emotional support but also educational support for patients that have a diagnosis of bladder cancer and now, rare bladder tumors.” Dr. Spiess offered similar advice for clinicians managing patients with rare GU tumors. He emphasized the key role played by patient advocacy groups, and recommended referral to institutions specializing in specific GU tumor types. For example, he recommended that patients with penile cancer be treated at Moffitt (Tampa) or MD Anderson (Houston), as these centers have the greatest relevant experience. Dr. McGregor disclosed relationships with Bayer, Astellas, Nektar, and others. Dr. Apolo and Dr. Spiess disclosed no conflicts of interest.
References
1.Necchi A et al. Eur Urol. 2021 June;79:S929-30.
2.Apolo AB et al. J Clin Oncol. 2021;39(6_suppl):3.
3.McGregor BA et al. Cancer. 2021 Mar 15;127(6):840-9.
4.McGregor BA and Sonpavde GP. Eur Urol Focus. 2020;6(1):14-16.5.Le Tourneau C et al. J Immunother Cancer. 2018 Oct 22;6(1):111.6.Naing A et al. J Immunother Cancer. 2020;8(1).
7.Raj N et al. J Clin Oncol. 2020;38(1):71-80.
8.Adra N et al. Ann Oncol. 2018;29(1):209-14.
9.Necchi A et al. Eur Urol. 2019;75(1):201-3.
In a field of poor outcomes, few standards of care, and small populations of patients scattered across the world, investigators studying rare genitourinary (GU) cancers are gaining ground through international collaboration and novel trial design.
Fundamental clinical questions in the area remain unanswered, including the value of conventional treatments, such as chemotherapy and surgery, vs. emerging immunotherapy combinations.
Managing patients with rare GU cancers presents a variety of challenges, as does conducting research in the field, according to Philippe E. Spiess, MD, MS, FACS, assistant chief of surgical services and senior member in the department of GU oncology at Moffitt Cancer Center, Tampa.
“Unfortunately, there are limited resources for patients – from an education, from a patient advocacy, and ultimately also from a research standpoint,” Dr. Spiess said in an interview, noting difficulties in attaining funding and reaching meaningful endpoints.
The Global Society of Rare Genitourinary Tumors
Last year Dr. Spiess teamed up with Andrea Necchi, MD, of the department of medical oncology at Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, to found the Global Society of Rare Genitourinary Tumors (GSRGT), the first organization of its kind.
“We’ve formally established a society and gotten some of the world leaders [in the field] … to work with us in developing educational tools and patient advocacy efforts to really promote and improve the care of patients impacted with rare cancers,” Dr. Spiess said.
He went on to highlight the truly global makeup of GSRGT, which includes members from leading centers in North America, South America, Europe, and India, and described it as a “grass-roots” organization that he and Dr. Necchi privately funded without financial backing from pharmaceutical companies.
The first GSRGT summit took place in 2020; it focused on penile and testis cancers and was attended by more than 350 participants. The second summit, planned for March 2022, in a virtual format, will focus on rare kidney cancers and upper tract cancers.
“We’ll definitely be having a lot of important conversations about important unmet needs, and some of the important clinical trials that patients and clinicians should be aware of,” Dr. Spiess said.
Dr. Spiess is currently involved in the International Penile Advanced Cancer Trial(InPACT), which is aiming to enroll 200 patients with squamous cell carcinoma of the penis. The randomized study will compare outcomes across patients treated with standard surgery alone, neoadjuvant chemotherapy plus surgery, and neoadjuvant chemoradiotherapy plus surgery.
“I think this is going to be a landmark study because it’s going to give really baseline high-quality data on the effectiveness of these therapies,” Dr. Spiess said.
Results are expected in 2024.
Basket trials open doors for patients in need
Other investigators are testing immunotherapy combinations in patients with rare GU tumors via nonrandomized basket trials, which widen inclusion criteria and improve local availability.
According to Bradley McGregor, MD, clinical director of the Lank Center for GU Oncology at the Dana-Farber Cancer Institute in Boston, early results from these trials are promising, both in terms of therapeutic efficacy and the approach itself.
“Patients [with rare GU tumors] would come to us saying, ‘Well, what can we do? What trial?’,” Dr. McGregor said. “But really, there was no trial to get them on.”Basket trials are therefore needed, he said, as they accelerate progress in the field and help meet patient needs.
“For some of these relatively rare diseases … there is no standard of care,” Dr. McGregor said. “And low incidence makes it challenging to conduct a dedicated clinical trial. Those patients are left with minimal therapeutic options. … We look to provide care for that unmet need.”Andrea B. Apolo, MD, described similar experiences as head of the bladder cancer section of the GU malignancies branch of the National Cancer Institute (NCI), Bethesda, Md.
“I’ve been at the NCI for the past 10 years and I’ve gotten a lot of referrals for rare tumors,” Dr. Apolo said. “[These patients] have tried all available standard of care options, and therefore are often looking for clinical trials and new drugs – any kind of therapy that may be effective for their disease.”This call for help, along with a growing scientific curiosity, motivated Dr. Apolo to design trials that would include patients who had nowhere else to go.
“I became very interested in … understanding more about the mechanism of tumorigenesis and understanding rare tumors, biologically, within the lab,” she said, “but also clinically, in terms of finding more effective therapies.”
Both Dr. McGregor and Dr. Apolo are currently conducting basket trials for patients with rare GU tumors. While Dr. McGregor is testing a combination of PD-1 inhibitor nivolumab and CTLA-4 inhibitor ipilimumab, Dr. Apolo is exploring the benefit of cabozantinib, a targeted therapy, given with either nivolumab or nivolumab plus ipilimumab.
When asked about these trials, Dr. Spiess said that “basket trials are important because they may give us an understanding of some potentially useful therapies or combinations;” however, he also pointed out their limitations, noting that they may inaccurately characterize the efficacy of given therapies over a broad array of disease entities even if they are of similar histology. As an example, he noted “very different” genomic profiles across squamous cell carcinomas of the pelvis depending on exact anatomical location, suggesting that these differences may affect responses to therapy, citing a recent study in European Urology that he conducted with Dr. Necchi.1
“[Basket trials] are probably not going to be the be-all-end-all,” Dr. Spiess said. “It really requires a global initiative to do these types of studies, which the Global Society of Rare Genitourinary Tumors will allow.”
Exploring immunotherapy combinations
Despite the potential limitations, recent basket trials involving immunotherapy regimens have been associated with overall response rates, in some subgroups, that exceed 35%.2,3
In comparison with previous trials, many of which had response rates in the single digits, or no responses at all, these results are, in Dr. McGregor’s words, “very thought provoking.”Most rare GU malignancies fall into one of four categories: bladder cancer variant histology (BCVH), adrenal tumors, penile squamous cell carcinoma (PSCC), and chemotherapy-refractory germ cell tumors (CRGCT). Among these, BCVH has the strongest evidence supporting clinical use of immunotherapy, based on U.S. approval for urothelial histology, according to Dr. McGregor.4Data supporting immunotherapy for the remaining disease subtypes are scarce. Although pembrolizumab is approved for patients with solid tumors that exhibit microsatellite instability (MSI), MSI is uncommon among patients with rare GU cancers; estimated incidence rates are less than 10%.4
“As such, clinical trials to address this unmet need are imperative,” Dr. McGregor wrote in a recent review article.4
According to Dr. McGregor, programmed death ligand 1 (PD-L1) expression in rare GU tumors may be relatively common in some disease subtypes, such as PSCC, which has a PD-L1 expression rate of up to 60%.4
But rare GU tumor trials involving a single checkpoint inhibitor have produced limited results, if any.
The largest trial for adrenocortical carcinoma (ACC), for example, which included 50 patients, showed that avelumab resulted in an objective response rate (ORR) of just 6%.5
Pembrolizumab was slightly more effective for ACC, based on a trial involving 39 patients, which returned an ORR of 23%, and another trial involving 15 patients that had a 15% ORR.6,7
Two other trials, which tested single-agent pembrolizumab or durvalumab in patients with CRGCT, resulted in no responses at all, whereas a trial testing pembrolizumab alone for penile squamous cell carcinoma was terminated in 2020, citing poor accrual.8,9 Still, the durvalumab trial for CRGCT, led by Dr. Necchi, did offer a glimpse at what might be possible with a combination of immunotherapies. Although no responses were observed among 11 patients who received durvalumab alone, an efficacy signal was observed in a second cohort of 11 patients who were given durvalumab in combination with the CTLA-4 inhibitor tremilimumab.9
Out of those 11 patients, 1 had a partial response, and another achieved stable disease.
In light of these findings, and more that have been published since then, the clinical trial landscape for rare GU tumors is shifting toward a combination immunotherapy approach, according to Dr. McGregor.4
Nivolumab and ipilimumab
Dr. McGregor is leading a phase II trial (NCT03333616) testing a combination of nivolumab and ipilimumab in patients with a variety of advanced rare GU malignancies, including bladder and upper tract carcinoma of variant histology (BUTCVH), adrenal tumors, CRGCT, PSCC, and prostate cancer of variant histology (PCVH).
“When trials are designed, these patients are often forgotten,” Dr. McGregor noted. “We said, let’s do a trial for all rare GU tumors and just sort of assess and look for a signal, and, hopefully, find a signal that we can then take to the next level.”
Along with appropriate disease phenotype, trial eligibility depended upon an ECOG performance status of 0-2 and no prior exposure to checkpoint inhibitors. Treatment-naive patients were allowed. All participants received nivolumab 3 mg/kg and ipilimumab 1 mg/kg IV every 3 weeks for four doses, followed by maintenance nivolumab at a dose of 480 mg every 4 weeks.
Most recent results, published in Cancer, included data from 55 patients, including 19 with BUTCVH, 18 with adrenal tumors, and 18 with other tumors.3 After a median follow-up of 9.9 months, 28 patients (51%) received all four doses of the regimen, 25 of whom received maintenance therapy with a median of four cycles.
Overall, nine patients (16%) responded to therapy, six of whom (67%) maintained their response for at least 9 months. Two responses were complete, and seven were partial. Median progression-free survival was 2.8 months.
Twenty-two patients (39%) had grade 3 or higher treatment-related adverse events, approximately one-quarter (23%) needed high-dose steroids, and a slightly greater proportion (27%) discontinued the regimen because of adverse events. Three patients exhibited grade 5 toxicity, and one patient death was treatment related. A closer look at the efficacy data suggested that one disease subgroup benefited much more than the others. The overall response rate among 19 patients with BUTCVH was 37%, compared with 6% in the other two cohorts.
“A response rate of 37% compares quite favorably to anything we’ve seen to date,” Dr. McGregor said. “It’s remarkable that [this response] was seen across histologies – we saw this in urachal, we saw this in adenocarcinoma – we really saw this across the board. This is very, very, very intriguing data.”
The phase II trial is ongoing at multiple centers across the country, including the Dana-Farber/Harvard Cancer Center, Boston, the University of Texas MD Anderson Cancer Center, Houston, the Moores Cancer Center at University of California Health, San Diego, the Ohio State University Comprehensive Cancer Center, Columbus, and the Winship Cancer Institute of Emory University, Atlanta.
“We accrued this trial in just under 18 months,” Dr. McGregor said. “I think this shows that with a well-designed trial, we can actually study these diseases and improve outcomes in these patients.” According to Dr. McGregor, the current findings deserve further investigation, potentially including expansion of the BUTCVH cohort. Recruitment is ongoing for a fourth cohort involving patients with tumors that exhibit neuroendocrine differentiation.
Cabozantinib and nivolumab with or without ipilimumab
Dr. Apolo is leading a similar basket trial (NCT02496208) that is testing cabozantinib plus nivolumab with or without ipilimumab.
“What we’re doing is using immunotherapy and a targeted therapy that work in standard urothelial carcinoma and renal cell carcinoma,” Dr. Apolo said. “But really, we don’t know the activity in these rare GU tumors. … There’s still so much we don’t understand about what the driving mutations are, and how we can best target them.”
Most recent data, published in Journal of Clinical Oncology, include 122 patients with metastatic GU tumors, including urothelial carcinoma, clear cell renal cell carcinoma, bladder adenocarcinoma, and other rare GU cancers.2
Among these patients, 54 were in the phase I dose-finding cohort (eight escalating doses) and 64 were in the dose-expansion cohorts.
After a median follow-up of 40.4 months, 64 patients received the dual combination, whereas 56 received the triplet regimen. The ORR for 108 evaluable patients was 38%, including 12 complete responses (11.1%) and 29 partial responses (26.9%). The largest disease cohort, for urothelial carcinoma, included 33 patients and was associated with an ORR of 42.4%, with a complete response rate of 21.2%. Objective response rate was highest for squamous bladder cancer (85.7%; n = 7), followed by clear cell renal carcinoma (62.5%; n = 16), renal medullary cancer (50%; n = 2), penile cancer (44.4%; n = 9), small cell bladder cancer (33.1%; n = 3), bladder adenocarcinoma (20%; n = 15), and prostate cancer (11.1%; n = 9). No responses were seen in six patients with germ cell tumors.
Adding ipilimumab appeared to have a minimal impact on toxicity. Grade 3 or 4 treatment-related adverse events (AEs) occurred in 84% of patients in the dual combination group, compared with 80% receiving the triplet regimen. Most common AEs were hypophosphatemia (16-25%), lipase elevation (20%), fatigue (18-20%), ALT elevation (5-14%), AST elevation (9-11%), diarrhea (9-11%), and thromboembolic event (4-11%). One patient taking the triplet regimen had grade 5 pneumonitis.
These positive phase I results have paved the way for the phase II ICONIC trial (NCT03866382), a national study available through the Alliance Cooperative Group. The trial is currently recruiting, with an estimated enrollment of 224 patients with rare GU tumors.
The ICONIC trial is just one of several studies that Dr. Apolo is conducting for patients with rare GU cancer. “I have several bladder cancer trials where I’m accepting rare GU tumors to enroll,” she said, noting that efficacy signals in these exploratory cohorts may be pursued with expansion studies like ICONIC.
This inclusive strategy is uncovering promising new treatments for some rare GU malignancies, but the rarest of the rare tumor types remain challenging to study, Dr. Apolo said, because very small sample sizes can preclude significant data. “Although we do have the referral base at the NCI, we still get a small number of a lot of rare tumors,” Dr. Apolo said. “What I end up having, a lot of time, are small subsets of rare tumors – I’ll have 4 of one kind, 10 of another.” This situation means that sometimes, time and resources must be focused where they are needed most.
“Sometimes I actually have to decide which are the more common rare tumors so I can study them in a larger cohort,” Dr. Apolo said. “It can have more clinical impact within the community of that rare tumor.” Dr. Apolo described the inherent conflict involved in this decision, but also, its ultimate necessity.
“It’s what you don’t want to do, but you end up doing,” she said. “Because you want to be inclusive and include the rare, rare tumor, but sometimes you just can’t get enough numbers to see if there’s actually a difference [in efficacy]. If it doesn’t work in one patient, does that mean it doesn’t work at all? You need more numbers to really test the efficacy of therapy.”
From clinical trials to clinical practice
To accrue the number of patients needed for practice-altering findings, both Dr. McGregor and Dr. Apolo emphasized the importance of institutional support and collaborative trial designs.
“The FDA is a great ally,” Dr. McGregor said. “They’re acutely aware of the challenges facing patients with rare malignancies – not just GU malignancies. They’re continuing to evaluate the best way to move these drugs forward for those patients. … They’re constantly working with investigators, with industry, looking at data and trying to determine at what threshold these will be practice-changing studies.”
Dr. McGregor suggested that larger trials could shift national guideline recommendations toward combination immunotherapies for patients with rare GU tumors, which would lead to inclusion in compendia, and from there, broader clinical usage.
“At end of the day, luckily, we’re not dealing with drugs that aren’t available,” Dr. McGregor said. “These are drugs that are readily available, approved by the FDA in other settings.”
Dr. Apolo also described strong support from the NCI.
“The NCI really encourages the conduction and enrollment of these rare GU tumor trials, because they understand that the NCI is a really good place to study these rare tumors,” she said. “We have unique resources that make it feasible to conduct some of these trials.”
Dr. Apolo also praised the Alliance Cooperative Group for helping expand patient access to rare GU tumor trials.
“[The Alliance Cooperative Group] makes trials available at community centers across the country,” Dr. Apolo said. “Patients don’t have to travel to the NCI, and they can get the same therapies.”
Still, Dr. Apolo recommended that, when possible, clinicians refer patients with newly diagnosed, rare GU tumors to centers that see a higher number of such cases.
“It’s hard to keep up with all the different treatments that are available right now for different cancers,” Dr. Apolo said. “And sometimes for the rare tumors, there may be great opportunities within a clinical trial that a cancer center may have available that may not be available locally in the community.”
For patients who would like to learn more about rare bladder cancers, Dr. Apolo recommended a visit to the Bladder Cancer Advocacy Network (BCAN) website (bcan.org).
“I’m a big fan of these patient-centered advocacy networks,” Dr. Apolo said. “I like BCAN a lot. It’s a patient-run organization for patients with bladder cancer. With them, I have done a couple of webinars for rare bladder tumors that Ive had some patients tell me are very helpful. They’re a terrific organization that really provides not only emotional support but also educational support for patients that have a diagnosis of bladder cancer and now, rare bladder tumors.” Dr. Spiess offered similar advice for clinicians managing patients with rare GU tumors. He emphasized the key role played by patient advocacy groups, and recommended referral to institutions specializing in specific GU tumor types. For example, he recommended that patients with penile cancer be treated at Moffitt (Tampa) or MD Anderson (Houston), as these centers have the greatest relevant experience. Dr. McGregor disclosed relationships with Bayer, Astellas, Nektar, and others. Dr. Apolo and Dr. Spiess disclosed no conflicts of interest.
References
1.Necchi A et al. Eur Urol. 2021 June;79:S929-30.
2.Apolo AB et al. J Clin Oncol. 2021;39(6_suppl):3.
3.McGregor BA et al. Cancer. 2021 Mar 15;127(6):840-9.
4.McGregor BA and Sonpavde GP. Eur Urol Focus. 2020;6(1):14-16.5.Le Tourneau C et al. J Immunother Cancer. 2018 Oct 22;6(1):111.6.Naing A et al. J Immunother Cancer. 2020;8(1).
7.Raj N et al. J Clin Oncol. 2020;38(1):71-80.
8.Adra N et al. Ann Oncol. 2018;29(1):209-14.
9.Necchi A et al. Eur Urol. 2019;75(1):201-3.
In a field of poor outcomes, few standards of care, and small populations of patients scattered across the world, investigators studying rare genitourinary (GU) cancers are gaining ground through international collaboration and novel trial design.
Fundamental clinical questions in the area remain unanswered, including the value of conventional treatments, such as chemotherapy and surgery, vs. emerging immunotherapy combinations.
Managing patients with rare GU cancers presents a variety of challenges, as does conducting research in the field, according to Philippe E. Spiess, MD, MS, FACS, assistant chief of surgical services and senior member in the department of GU oncology at Moffitt Cancer Center, Tampa.
“Unfortunately, there are limited resources for patients – from an education, from a patient advocacy, and ultimately also from a research standpoint,” Dr. Spiess said in an interview, noting difficulties in attaining funding and reaching meaningful endpoints.
The Global Society of Rare Genitourinary Tumors
Last year Dr. Spiess teamed up with Andrea Necchi, MD, of the department of medical oncology at Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, to found the Global Society of Rare Genitourinary Tumors (GSRGT), the first organization of its kind.
“We’ve formally established a society and gotten some of the world leaders [in the field] … to work with us in developing educational tools and patient advocacy efforts to really promote and improve the care of patients impacted with rare cancers,” Dr. Spiess said.
He went on to highlight the truly global makeup of GSRGT, which includes members from leading centers in North America, South America, Europe, and India, and described it as a “grass-roots” organization that he and Dr. Necchi privately funded without financial backing from pharmaceutical companies.
The first GSRGT summit took place in 2020; it focused on penile and testis cancers and was attended by more than 350 participants. The second summit, planned for March 2022, in a virtual format, will focus on rare kidney cancers and upper tract cancers.
“We’ll definitely be having a lot of important conversations about important unmet needs, and some of the important clinical trials that patients and clinicians should be aware of,” Dr. Spiess said.
Dr. Spiess is currently involved in the International Penile Advanced Cancer Trial(InPACT), which is aiming to enroll 200 patients with squamous cell carcinoma of the penis. The randomized study will compare outcomes across patients treated with standard surgery alone, neoadjuvant chemotherapy plus surgery, and neoadjuvant chemoradiotherapy plus surgery.
“I think this is going to be a landmark study because it’s going to give really baseline high-quality data on the effectiveness of these therapies,” Dr. Spiess said.
Results are expected in 2024.
Basket trials open doors for patients in need
Other investigators are testing immunotherapy combinations in patients with rare GU tumors via nonrandomized basket trials, which widen inclusion criteria and improve local availability.
According to Bradley McGregor, MD, clinical director of the Lank Center for GU Oncology at the Dana-Farber Cancer Institute in Boston, early results from these trials are promising, both in terms of therapeutic efficacy and the approach itself.
“Patients [with rare GU tumors] would come to us saying, ‘Well, what can we do? What trial?’,” Dr. McGregor said. “But really, there was no trial to get them on.”Basket trials are therefore needed, he said, as they accelerate progress in the field and help meet patient needs.
“For some of these relatively rare diseases … there is no standard of care,” Dr. McGregor said. “And low incidence makes it challenging to conduct a dedicated clinical trial. Those patients are left with minimal therapeutic options. … We look to provide care for that unmet need.”Andrea B. Apolo, MD, described similar experiences as head of the bladder cancer section of the GU malignancies branch of the National Cancer Institute (NCI), Bethesda, Md.
“I’ve been at the NCI for the past 10 years and I’ve gotten a lot of referrals for rare tumors,” Dr. Apolo said. “[These patients] have tried all available standard of care options, and therefore are often looking for clinical trials and new drugs – any kind of therapy that may be effective for their disease.”This call for help, along with a growing scientific curiosity, motivated Dr. Apolo to design trials that would include patients who had nowhere else to go.
“I became very interested in … understanding more about the mechanism of tumorigenesis and understanding rare tumors, biologically, within the lab,” she said, “but also clinically, in terms of finding more effective therapies.”
Both Dr. McGregor and Dr. Apolo are currently conducting basket trials for patients with rare GU tumors. While Dr. McGregor is testing a combination of PD-1 inhibitor nivolumab and CTLA-4 inhibitor ipilimumab, Dr. Apolo is exploring the benefit of cabozantinib, a targeted therapy, given with either nivolumab or nivolumab plus ipilimumab.
When asked about these trials, Dr. Spiess said that “basket trials are important because they may give us an understanding of some potentially useful therapies or combinations;” however, he also pointed out their limitations, noting that they may inaccurately characterize the efficacy of given therapies over a broad array of disease entities even if they are of similar histology. As an example, he noted “very different” genomic profiles across squamous cell carcinomas of the pelvis depending on exact anatomical location, suggesting that these differences may affect responses to therapy, citing a recent study in European Urology that he conducted with Dr. Necchi.1
“[Basket trials] are probably not going to be the be-all-end-all,” Dr. Spiess said. “It really requires a global initiative to do these types of studies, which the Global Society of Rare Genitourinary Tumors will allow.”
Exploring immunotherapy combinations
Despite the potential limitations, recent basket trials involving immunotherapy regimens have been associated with overall response rates, in some subgroups, that exceed 35%.2,3
In comparison with previous trials, many of which had response rates in the single digits, or no responses at all, these results are, in Dr. McGregor’s words, “very thought provoking.”Most rare GU malignancies fall into one of four categories: bladder cancer variant histology (BCVH), adrenal tumors, penile squamous cell carcinoma (PSCC), and chemotherapy-refractory germ cell tumors (CRGCT). Among these, BCVH has the strongest evidence supporting clinical use of immunotherapy, based on U.S. approval for urothelial histology, according to Dr. McGregor.4Data supporting immunotherapy for the remaining disease subtypes are scarce. Although pembrolizumab is approved for patients with solid tumors that exhibit microsatellite instability (MSI), MSI is uncommon among patients with rare GU cancers; estimated incidence rates are less than 10%.4
“As such, clinical trials to address this unmet need are imperative,” Dr. McGregor wrote in a recent review article.4
According to Dr. McGregor, programmed death ligand 1 (PD-L1) expression in rare GU tumors may be relatively common in some disease subtypes, such as PSCC, which has a PD-L1 expression rate of up to 60%.4
But rare GU tumor trials involving a single checkpoint inhibitor have produced limited results, if any.
The largest trial for adrenocortical carcinoma (ACC), for example, which included 50 patients, showed that avelumab resulted in an objective response rate (ORR) of just 6%.5
Pembrolizumab was slightly more effective for ACC, based on a trial involving 39 patients, which returned an ORR of 23%, and another trial involving 15 patients that had a 15% ORR.6,7
Two other trials, which tested single-agent pembrolizumab or durvalumab in patients with CRGCT, resulted in no responses at all, whereas a trial testing pembrolizumab alone for penile squamous cell carcinoma was terminated in 2020, citing poor accrual.8,9 Still, the durvalumab trial for CRGCT, led by Dr. Necchi, did offer a glimpse at what might be possible with a combination of immunotherapies. Although no responses were observed among 11 patients who received durvalumab alone, an efficacy signal was observed in a second cohort of 11 patients who were given durvalumab in combination with the CTLA-4 inhibitor tremilimumab.9
Out of those 11 patients, 1 had a partial response, and another achieved stable disease.
In light of these findings, and more that have been published since then, the clinical trial landscape for rare GU tumors is shifting toward a combination immunotherapy approach, according to Dr. McGregor.4
Nivolumab and ipilimumab
Dr. McGregor is leading a phase II trial (NCT03333616) testing a combination of nivolumab and ipilimumab in patients with a variety of advanced rare GU malignancies, including bladder and upper tract carcinoma of variant histology (BUTCVH), adrenal tumors, CRGCT, PSCC, and prostate cancer of variant histology (PCVH).
“When trials are designed, these patients are often forgotten,” Dr. McGregor noted. “We said, let’s do a trial for all rare GU tumors and just sort of assess and look for a signal, and, hopefully, find a signal that we can then take to the next level.”
Along with appropriate disease phenotype, trial eligibility depended upon an ECOG performance status of 0-2 and no prior exposure to checkpoint inhibitors. Treatment-naive patients were allowed. All participants received nivolumab 3 mg/kg and ipilimumab 1 mg/kg IV every 3 weeks for four doses, followed by maintenance nivolumab at a dose of 480 mg every 4 weeks.
Most recent results, published in Cancer, included data from 55 patients, including 19 with BUTCVH, 18 with adrenal tumors, and 18 with other tumors.3 After a median follow-up of 9.9 months, 28 patients (51%) received all four doses of the regimen, 25 of whom received maintenance therapy with a median of four cycles.
Overall, nine patients (16%) responded to therapy, six of whom (67%) maintained their response for at least 9 months. Two responses were complete, and seven were partial. Median progression-free survival was 2.8 months.
Twenty-two patients (39%) had grade 3 or higher treatment-related adverse events, approximately one-quarter (23%) needed high-dose steroids, and a slightly greater proportion (27%) discontinued the regimen because of adverse events. Three patients exhibited grade 5 toxicity, and one patient death was treatment related. A closer look at the efficacy data suggested that one disease subgroup benefited much more than the others. The overall response rate among 19 patients with BUTCVH was 37%, compared with 6% in the other two cohorts.
“A response rate of 37% compares quite favorably to anything we’ve seen to date,” Dr. McGregor said. “It’s remarkable that [this response] was seen across histologies – we saw this in urachal, we saw this in adenocarcinoma – we really saw this across the board. This is very, very, very intriguing data.”
The phase II trial is ongoing at multiple centers across the country, including the Dana-Farber/Harvard Cancer Center, Boston, the University of Texas MD Anderson Cancer Center, Houston, the Moores Cancer Center at University of California Health, San Diego, the Ohio State University Comprehensive Cancer Center, Columbus, and the Winship Cancer Institute of Emory University, Atlanta.
“We accrued this trial in just under 18 months,” Dr. McGregor said. “I think this shows that with a well-designed trial, we can actually study these diseases and improve outcomes in these patients.” According to Dr. McGregor, the current findings deserve further investigation, potentially including expansion of the BUTCVH cohort. Recruitment is ongoing for a fourth cohort involving patients with tumors that exhibit neuroendocrine differentiation.
Cabozantinib and nivolumab with or without ipilimumab
Dr. Apolo is leading a similar basket trial (NCT02496208) that is testing cabozantinib plus nivolumab with or without ipilimumab.
“What we’re doing is using immunotherapy and a targeted therapy that work in standard urothelial carcinoma and renal cell carcinoma,” Dr. Apolo said. “But really, we don’t know the activity in these rare GU tumors. … There’s still so much we don’t understand about what the driving mutations are, and how we can best target them.”
Most recent data, published in Journal of Clinical Oncology, include 122 patients with metastatic GU tumors, including urothelial carcinoma, clear cell renal cell carcinoma, bladder adenocarcinoma, and other rare GU cancers.2
Among these patients, 54 were in the phase I dose-finding cohort (eight escalating doses) and 64 were in the dose-expansion cohorts.
After a median follow-up of 40.4 months, 64 patients received the dual combination, whereas 56 received the triplet regimen. The ORR for 108 evaluable patients was 38%, including 12 complete responses (11.1%) and 29 partial responses (26.9%). The largest disease cohort, for urothelial carcinoma, included 33 patients and was associated with an ORR of 42.4%, with a complete response rate of 21.2%. Objective response rate was highest for squamous bladder cancer (85.7%; n = 7), followed by clear cell renal carcinoma (62.5%; n = 16), renal medullary cancer (50%; n = 2), penile cancer (44.4%; n = 9), small cell bladder cancer (33.1%; n = 3), bladder adenocarcinoma (20%; n = 15), and prostate cancer (11.1%; n = 9). No responses were seen in six patients with germ cell tumors.
Adding ipilimumab appeared to have a minimal impact on toxicity. Grade 3 or 4 treatment-related adverse events (AEs) occurred in 84% of patients in the dual combination group, compared with 80% receiving the triplet regimen. Most common AEs were hypophosphatemia (16-25%), lipase elevation (20%), fatigue (18-20%), ALT elevation (5-14%), AST elevation (9-11%), diarrhea (9-11%), and thromboembolic event (4-11%). One patient taking the triplet regimen had grade 5 pneumonitis.
These positive phase I results have paved the way for the phase II ICONIC trial (NCT03866382), a national study available through the Alliance Cooperative Group. The trial is currently recruiting, with an estimated enrollment of 224 patients with rare GU tumors.
The ICONIC trial is just one of several studies that Dr. Apolo is conducting for patients with rare GU cancer. “I have several bladder cancer trials where I’m accepting rare GU tumors to enroll,” she said, noting that efficacy signals in these exploratory cohorts may be pursued with expansion studies like ICONIC.
This inclusive strategy is uncovering promising new treatments for some rare GU malignancies, but the rarest of the rare tumor types remain challenging to study, Dr. Apolo said, because very small sample sizes can preclude significant data. “Although we do have the referral base at the NCI, we still get a small number of a lot of rare tumors,” Dr. Apolo said. “What I end up having, a lot of time, are small subsets of rare tumors – I’ll have 4 of one kind, 10 of another.” This situation means that sometimes, time and resources must be focused where they are needed most.
“Sometimes I actually have to decide which are the more common rare tumors so I can study them in a larger cohort,” Dr. Apolo said. “It can have more clinical impact within the community of that rare tumor.” Dr. Apolo described the inherent conflict involved in this decision, but also, its ultimate necessity.
“It’s what you don’t want to do, but you end up doing,” she said. “Because you want to be inclusive and include the rare, rare tumor, but sometimes you just can’t get enough numbers to see if there’s actually a difference [in efficacy]. If it doesn’t work in one patient, does that mean it doesn’t work at all? You need more numbers to really test the efficacy of therapy.”
From clinical trials to clinical practice
To accrue the number of patients needed for practice-altering findings, both Dr. McGregor and Dr. Apolo emphasized the importance of institutional support and collaborative trial designs.
“The FDA is a great ally,” Dr. McGregor said. “They’re acutely aware of the challenges facing patients with rare malignancies – not just GU malignancies. They’re continuing to evaluate the best way to move these drugs forward for those patients. … They’re constantly working with investigators, with industry, looking at data and trying to determine at what threshold these will be practice-changing studies.”
Dr. McGregor suggested that larger trials could shift national guideline recommendations toward combination immunotherapies for patients with rare GU tumors, which would lead to inclusion in compendia, and from there, broader clinical usage.
“At end of the day, luckily, we’re not dealing with drugs that aren’t available,” Dr. McGregor said. “These are drugs that are readily available, approved by the FDA in other settings.”
Dr. Apolo also described strong support from the NCI.
“The NCI really encourages the conduction and enrollment of these rare GU tumor trials, because they understand that the NCI is a really good place to study these rare tumors,” she said. “We have unique resources that make it feasible to conduct some of these trials.”
Dr. Apolo also praised the Alliance Cooperative Group for helping expand patient access to rare GU tumor trials.
“[The Alliance Cooperative Group] makes trials available at community centers across the country,” Dr. Apolo said. “Patients don’t have to travel to the NCI, and they can get the same therapies.”
Still, Dr. Apolo recommended that, when possible, clinicians refer patients with newly diagnosed, rare GU tumors to centers that see a higher number of such cases.
“It’s hard to keep up with all the different treatments that are available right now for different cancers,” Dr. Apolo said. “And sometimes for the rare tumors, there may be great opportunities within a clinical trial that a cancer center may have available that may not be available locally in the community.”
For patients who would like to learn more about rare bladder cancers, Dr. Apolo recommended a visit to the Bladder Cancer Advocacy Network (BCAN) website (bcan.org).
“I’m a big fan of these patient-centered advocacy networks,” Dr. Apolo said. “I like BCAN a lot. It’s a patient-run organization for patients with bladder cancer. With them, I have done a couple of webinars for rare bladder tumors that Ive had some patients tell me are very helpful. They’re a terrific organization that really provides not only emotional support but also educational support for patients that have a diagnosis of bladder cancer and now, rare bladder tumors.” Dr. Spiess offered similar advice for clinicians managing patients with rare GU tumors. He emphasized the key role played by patient advocacy groups, and recommended referral to institutions specializing in specific GU tumor types. For example, he recommended that patients with penile cancer be treated at Moffitt (Tampa) or MD Anderson (Houston), as these centers have the greatest relevant experience. Dr. McGregor disclosed relationships with Bayer, Astellas, Nektar, and others. Dr. Apolo and Dr. Spiess disclosed no conflicts of interest.
References
1.Necchi A et al. Eur Urol. 2021 June;79:S929-30.
2.Apolo AB et al. J Clin Oncol. 2021;39(6_suppl):3.
3.McGregor BA et al. Cancer. 2021 Mar 15;127(6):840-9.
4.McGregor BA and Sonpavde GP. Eur Urol Focus. 2020;6(1):14-16.5.Le Tourneau C et al. J Immunother Cancer. 2018 Oct 22;6(1):111.6.Naing A et al. J Immunother Cancer. 2020;8(1).
7.Raj N et al. J Clin Oncol. 2020;38(1):71-80.
8.Adra N et al. Ann Oncol. 2018;29(1):209-14.
9.Necchi A et al. Eur Urol. 2019;75(1):201-3.