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The study included 70 patients who received lenvatinib in combination with pembrolizumab. Patients who were started on 14 mg of lenvatinib per day had fewer dose reductions and a longer time to the first dose reduction, compared with patients who were started on the recommended 20-mg dose. There were no significant differences in response, progression-free survival, or overall survival between the two dose groups.
“Published studies and these results may support using lenvatinib at a starting dose of 14 mg daily in clinical practice,” said Jeffrey How, MD, a gynecologic oncology fellow at MD Anderson Cancer Center in Houston.
Dr. How presented the results at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 10775).
This is not the first time a recommended starting dose has been deemed too high to use in practice, according to Carol Aghajanian, MD, chief of gynecologic medical oncology at Memorial Sloan Kettering Cancer Center in New York and a panelist for the session where Dr. How presented his research.
Dr. Aghajanian noted that pegylated liposomal doxorubicin and topotecan are “rarely, if ever” started at the labeling doses for recurrent ovarian cancer. Those doses proved to be too high for general practice and “not tolerable with multicycle treatment,” she said.
“We may again be experiencing the effect of single-cycle, dose-limiting toxicity information not guiding us well in how to treat patients over time,” she added.
Study rationale
Based on a 38% overall response rate in the phase 2 KEYNOTE-146 trial, lenvatinib plus pembrolizumab was approved in September 2019 to treat patients with advanced endometrial carcinoma that is not microsatellite instability–high or mismatch repair deficient who have progressed on systemic therapy and are not candidates for curative surgery or radiation.
However, the rate of grade 3/4 adverse events with the combination was 66.9% in the trial, leading to dose interruptions or reductions and a discontinuation rate of 17.7%.
MD Anderson oncologists noticed similar toxicity rates at the approved lenvatinib dose of 20 mg per day when they started using the combination in October 2019. It raised a question about the feasibility of implementing the regimen in general practice as well as concerns about compliance, Dr. How said.
“As a consequence, our team started patients on a reduced dose of lenvatinib to improve safety and tolerability,” he added.
The mean dose intensity in the phase 2 trial was 14.4 mg/day, so the team began to start patients on 14 mg daily.
Results and implications
Of the 70 patients studied, 16 were started at 20 mg, and 54 were started at 14 mg. There were no significant differences between the two groups at baseline.
In the entire cohort, the median age was 65.5 years, and patients had received a median of two prior lines of therapy (range, one to nine). Most patients (90%) had a performance status of 0 or 1, 92.9% had microsatellite stable tumors, and 27.1% each had endometrioid or serous histology.
There was no significant difference between the dose groups with regard to any hospitalization (P = .46), hospitalization due to treatment-related adverse events (P = .55), dose interruption (P = .18), or treatment discontinuation due to treatment-related adverse events (P = .54).
However, the average number of dose reductions per patient was higher in the 20-mg group than in the 14-mg group – 1.1 and 0.4, respectively (P = .003).
The increased dose reductions with the higher starting dose were due mostly to gastrointestinal and hematologic adverse events as well as fatigue and anorexia, all of which were far more common in patients started at 20 mg.
Patients in the 14-mg group had a longer time to the first dose reduction or discontinuation due to toxicity – 107 days vs. 42 days in the 20-mg group (P = .001).
There was no significant difference in response rates between the 14-mg and 20-mg groups – 38.2% and 28.6%, respectively (P = .51) – and no significant difference in clinical benefit rates – 72.3% and 57.1%, respectively.
The median progression-free survival was 3.2 months in the 20-mg group and 5.5 months in the 14-mg group (P = .25). The median overall survival was 8.6 months and 10.3 months, respectively (P = .95).
Dr. How noted that this study was limited by its retrospective nature, and the small number of women started at 20 mg may have limited the ability to detect differences with a lower starting dose. Still, these results seem to support a starting dose of 14 mg, he concluded.
In a discussion after Dr. How’s presentation, panelist Judith Smith, PharmD, of UT Health in Houston, noted that her practice is starting women on lenvatinib at 12 mg per day.
“You can use the 14-mg convenience pack, but, from a cost perspective ... we have to be cognizant of the financial toxicity,” she said. “[Combining the] 10-mg and 4-mg tablets is going to be more expensive, so we’ve been using the 4-mg tablets [three per day] and starting at 12 mg.”
This study was funded by MD Anderson and the National Institutes of Health. Dr. How reported having no conflicts of interest. Dr. Aghajanian and Dr. Smith did not provide disclosures.
The study included 70 patients who received lenvatinib in combination with pembrolizumab. Patients who were started on 14 mg of lenvatinib per day had fewer dose reductions and a longer time to the first dose reduction, compared with patients who were started on the recommended 20-mg dose. There were no significant differences in response, progression-free survival, or overall survival between the two dose groups.
“Published studies and these results may support using lenvatinib at a starting dose of 14 mg daily in clinical practice,” said Jeffrey How, MD, a gynecologic oncology fellow at MD Anderson Cancer Center in Houston.
Dr. How presented the results at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 10775).
This is not the first time a recommended starting dose has been deemed too high to use in practice, according to Carol Aghajanian, MD, chief of gynecologic medical oncology at Memorial Sloan Kettering Cancer Center in New York and a panelist for the session where Dr. How presented his research.
Dr. Aghajanian noted that pegylated liposomal doxorubicin and topotecan are “rarely, if ever” started at the labeling doses for recurrent ovarian cancer. Those doses proved to be too high for general practice and “not tolerable with multicycle treatment,” she said.
“We may again be experiencing the effect of single-cycle, dose-limiting toxicity information not guiding us well in how to treat patients over time,” she added.
Study rationale
Based on a 38% overall response rate in the phase 2 KEYNOTE-146 trial, lenvatinib plus pembrolizumab was approved in September 2019 to treat patients with advanced endometrial carcinoma that is not microsatellite instability–high or mismatch repair deficient who have progressed on systemic therapy and are not candidates for curative surgery or radiation.
However, the rate of grade 3/4 adverse events with the combination was 66.9% in the trial, leading to dose interruptions or reductions and a discontinuation rate of 17.7%.
MD Anderson oncologists noticed similar toxicity rates at the approved lenvatinib dose of 20 mg per day when they started using the combination in October 2019. It raised a question about the feasibility of implementing the regimen in general practice as well as concerns about compliance, Dr. How said.
“As a consequence, our team started patients on a reduced dose of lenvatinib to improve safety and tolerability,” he added.
The mean dose intensity in the phase 2 trial was 14.4 mg/day, so the team began to start patients on 14 mg daily.
Results and implications
Of the 70 patients studied, 16 were started at 20 mg, and 54 were started at 14 mg. There were no significant differences between the two groups at baseline.
In the entire cohort, the median age was 65.5 years, and patients had received a median of two prior lines of therapy (range, one to nine). Most patients (90%) had a performance status of 0 or 1, 92.9% had microsatellite stable tumors, and 27.1% each had endometrioid or serous histology.
There was no significant difference between the dose groups with regard to any hospitalization (P = .46), hospitalization due to treatment-related adverse events (P = .55), dose interruption (P = .18), or treatment discontinuation due to treatment-related adverse events (P = .54).
However, the average number of dose reductions per patient was higher in the 20-mg group than in the 14-mg group – 1.1 and 0.4, respectively (P = .003).
The increased dose reductions with the higher starting dose were due mostly to gastrointestinal and hematologic adverse events as well as fatigue and anorexia, all of which were far more common in patients started at 20 mg.
Patients in the 14-mg group had a longer time to the first dose reduction or discontinuation due to toxicity – 107 days vs. 42 days in the 20-mg group (P = .001).
There was no significant difference in response rates between the 14-mg and 20-mg groups – 38.2% and 28.6%, respectively (P = .51) – and no significant difference in clinical benefit rates – 72.3% and 57.1%, respectively.
The median progression-free survival was 3.2 months in the 20-mg group and 5.5 months in the 14-mg group (P = .25). The median overall survival was 8.6 months and 10.3 months, respectively (P = .95).
Dr. How noted that this study was limited by its retrospective nature, and the small number of women started at 20 mg may have limited the ability to detect differences with a lower starting dose. Still, these results seem to support a starting dose of 14 mg, he concluded.
In a discussion after Dr. How’s presentation, panelist Judith Smith, PharmD, of UT Health in Houston, noted that her practice is starting women on lenvatinib at 12 mg per day.
“You can use the 14-mg convenience pack, but, from a cost perspective ... we have to be cognizant of the financial toxicity,” she said. “[Combining the] 10-mg and 4-mg tablets is going to be more expensive, so we’ve been using the 4-mg tablets [three per day] and starting at 12 mg.”
This study was funded by MD Anderson and the National Institutes of Health. Dr. How reported having no conflicts of interest. Dr. Aghajanian and Dr. Smith did not provide disclosures.
The study included 70 patients who received lenvatinib in combination with pembrolizumab. Patients who were started on 14 mg of lenvatinib per day had fewer dose reductions and a longer time to the first dose reduction, compared with patients who were started on the recommended 20-mg dose. There were no significant differences in response, progression-free survival, or overall survival between the two dose groups.
“Published studies and these results may support using lenvatinib at a starting dose of 14 mg daily in clinical practice,” said Jeffrey How, MD, a gynecologic oncology fellow at MD Anderson Cancer Center in Houston.
Dr. How presented the results at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 10775).
This is not the first time a recommended starting dose has been deemed too high to use in practice, according to Carol Aghajanian, MD, chief of gynecologic medical oncology at Memorial Sloan Kettering Cancer Center in New York and a panelist for the session where Dr. How presented his research.
Dr. Aghajanian noted that pegylated liposomal doxorubicin and topotecan are “rarely, if ever” started at the labeling doses for recurrent ovarian cancer. Those doses proved to be too high for general practice and “not tolerable with multicycle treatment,” she said.
“We may again be experiencing the effect of single-cycle, dose-limiting toxicity information not guiding us well in how to treat patients over time,” she added.
Study rationale
Based on a 38% overall response rate in the phase 2 KEYNOTE-146 trial, lenvatinib plus pembrolizumab was approved in September 2019 to treat patients with advanced endometrial carcinoma that is not microsatellite instability–high or mismatch repair deficient who have progressed on systemic therapy and are not candidates for curative surgery or radiation.
However, the rate of grade 3/4 adverse events with the combination was 66.9% in the trial, leading to dose interruptions or reductions and a discontinuation rate of 17.7%.
MD Anderson oncologists noticed similar toxicity rates at the approved lenvatinib dose of 20 mg per day when they started using the combination in October 2019. It raised a question about the feasibility of implementing the regimen in general practice as well as concerns about compliance, Dr. How said.
“As a consequence, our team started patients on a reduced dose of lenvatinib to improve safety and tolerability,” he added.
The mean dose intensity in the phase 2 trial was 14.4 mg/day, so the team began to start patients on 14 mg daily.
Results and implications
Of the 70 patients studied, 16 were started at 20 mg, and 54 were started at 14 mg. There were no significant differences between the two groups at baseline.
In the entire cohort, the median age was 65.5 years, and patients had received a median of two prior lines of therapy (range, one to nine). Most patients (90%) had a performance status of 0 or 1, 92.9% had microsatellite stable tumors, and 27.1% each had endometrioid or serous histology.
There was no significant difference between the dose groups with regard to any hospitalization (P = .46), hospitalization due to treatment-related adverse events (P = .55), dose interruption (P = .18), or treatment discontinuation due to treatment-related adverse events (P = .54).
However, the average number of dose reductions per patient was higher in the 20-mg group than in the 14-mg group – 1.1 and 0.4, respectively (P = .003).
The increased dose reductions with the higher starting dose were due mostly to gastrointestinal and hematologic adverse events as well as fatigue and anorexia, all of which were far more common in patients started at 20 mg.
Patients in the 14-mg group had a longer time to the first dose reduction or discontinuation due to toxicity – 107 days vs. 42 days in the 20-mg group (P = .001).
There was no significant difference in response rates between the 14-mg and 20-mg groups – 38.2% and 28.6%, respectively (P = .51) – and no significant difference in clinical benefit rates – 72.3% and 57.1%, respectively.
The median progression-free survival was 3.2 months in the 20-mg group and 5.5 months in the 14-mg group (P = .25). The median overall survival was 8.6 months and 10.3 months, respectively (P = .95).
Dr. How noted that this study was limited by its retrospective nature, and the small number of women started at 20 mg may have limited the ability to detect differences with a lower starting dose. Still, these results seem to support a starting dose of 14 mg, he concluded.
In a discussion after Dr. How’s presentation, panelist Judith Smith, PharmD, of UT Health in Houston, noted that her practice is starting women on lenvatinib at 12 mg per day.
“You can use the 14-mg convenience pack, but, from a cost perspective ... we have to be cognizant of the financial toxicity,” she said. “[Combining the] 10-mg and 4-mg tablets is going to be more expensive, so we’ve been using the 4-mg tablets [three per day] and starting at 12 mg.”
This study was funded by MD Anderson and the National Institutes of Health. Dr. How reported having no conflicts of interest. Dr. Aghajanian and Dr. Smith did not provide disclosures.
FROM SGO 2021