Outcomes by Retrospective Eligibility for Maintenance Therapy of Patients With Advanced Urothelial Carcinoma: Post Hoc Analysis of the Phase 3 KEYNOTE-361 Trial.

Introduction: The phase 3 KEYNOTE-361 trial of first-line pembrolizumab with or without chemotherapy versus chemotherapy alone in patients with locally advanced or metastatic urothelial carcinoma (la/mUC) completed enrollment before the approval of postchemotherapy maintenance avelumab for patients without progressive disease. This post hoc analysis evaluated the outcomes of patients who received chemotherapy alone in KEYNOTE-361 by retrospective eligibility for subsequent maintenance therapy.
Patients and Methods: Patients in the chemotherapy alone arm were retrospectively categorized as maintenance eligible (received ≥4 cycles of chemotherapy and did not die or experience disease progression within 10 weeks of chemotherapy completion), maintenance ineligible (received <4 cycles of chemotherapy or had progressive disease or died within 0-10 weeks after completion of ≥4 cycles of chemotherapy), and indeterminate eligibility for maintenance therapy (if neither maintenance eligible or ineligible). End points included progression-free survival per Response Evaluation Criteria in Solid Tumors version 1.1 by blinded independent central review and overall survival from randomization (start of chemotherapy).
Results: Median follow-up was 31.7 months (range, 22.0-42.3). Among 342 patients who received chemotherapy alone, 172 (50.3%) were maintenance eligible, 108 (31.6%) were maintenance ineligible, and 62 (18.1%) had indeterminate eligibility for maintenance therapy. The median progression-free survival was 9.0 months (95% CI 8.4-10.4) in maintenance-eligible patients, 5.1 months (4.2-6.0) in maintenance-ineligible patients, and 2.3 months (1.9-3.8) in the indeterminate group; median overall survival was 23.3 months (95% CI 19.4-26.1), 10.2 months (9.1-11.6), and 5.5 months (3.7-8.5), respectively.
Conclusion: This post hoc analysis suggests that a majority of patients with untreated la/mUC who initiated chemotherapy in a clinical trial may have been considered eligible for maintenance therapy and had favorable survival outcomes compared with those considered maintenance ineligible.
Competing Interests: Disclosure R. Mamtani reports research grants or contracts to his institution from Astellas and MSD and consulting fees from Astellas, Bristol Myers Squibb, Merck & Co, Inc, and Seagen outside the submitted work. N. Matsubara reports research grants or contracts to his institution from AbbVie, Amgen, Astellas, AstraZeneca, Bayer, Chugai, Eisai, Eli Lilly, Janssen, MSD, Pfizer, PRA Health Science, Roche, Taiho, Takeda, and Seagen; personal payment or honoraria from Sanofi; and support for attending meetings and/or travel from Pfizer outside the submitted work. A. Montesa Pino reports consulting fees from Advanced Accelerator Applications, Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Ipsen, Janssen, Merck & Co, Inc, MSD, Novartis, and Pfizer; support for attending meetings and/or travel from Bayer, Ipsen, Merck & Co, Inc, and Pfizer; and participation on a data safety monitoring board or advisory board of Advanced Accelerator Applications, Ipsen, and Merck & Co, Inc outside the submitted work. U. Anido Herranz reports payments for lectures from Ipsen and Merck & Co, Inc outside the submitted work. M. A. N. Şendur reports consulting fees and payments or honoraria from Astellas, AstraZeneca, Bristol Myers Squibb, Gilead, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, and Takeda. G. Gravis reports research grants or contracts to his institution from Bristol Myers Squibb and Janssen; payments or honoraria to his institution for lectures, presentations, speaker's bureaus, manuscript writing, or educational events from Advanced Accelerator Applications, Alliance Merck-Pfizer, Amgen, Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Eisai, Ipsen, Janssen, MSD, Pfizer, and Sanofi; support for attending meetings and/or travel from AstraZeneca, Bayer, Bristol Myers Squibb, Ipsen, Janssen, MSD, and Pfizer; and participation on a data safety monitoring board or advisory board of Advanced Accelerator Applications, Alliance Merck-Pfizer, AstraZeneca, Bayer, Bristol Myers Squibb, Eisai, Ipsen, Janssen, and Pfizer outside the submitted work. O. Huillard reports payments or honoraria to his institution for lectures, presentations, speaker's bureaus, manuscript writing or educational events from Advanced Accelerator Applications, Bristol Myers Squibb, Eisai, Ipsen, Janssen, MSD, Novartis, Pfizer, and Sanofi; and support for attending meetings and/or travel from Advanced Accelerator Applications and Ipsen outside the submitted work. R. Gafanov reports funding for the present manuscript from MSD; research grants or contracts to him and his institution from Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Ipsen, Jannsen, Pfizer, and Roche; payments or honoraria to him and his institution for lectures, presentations, speaker's bureaus, manuscript writing or educational events from Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Ipsen, Jannsen, Pfizer, and Roche; support for attending meetings and/or travel from Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Ipsen, Jannsen, Pfizer, and Roche; and participation on a data safety monitoring board or advisory board of Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Ipsen, Jannsen, Pfizer, and Roche outside the submitted work. F. Joly reports grants or contracts to her institution for ISS protocol from Ipsen; consulting fees paid to her for membership of scientific board of Esai Co, Ltd., Ipsen, and Pfizer; payment for lectures from Ipsen and Pfizer; and support for congress attendance from Esai Co, Ltd. and Ipsen. J. Bedke reports receiving medical writing support and local principal investigator payments to his institution for the present manuscript from MSD; local principal investigator payments to his institution from Astellas, AstraZeneca, Bristol Myers Squibb, Eisai, Ipsen, MSD, Nektar, Novartis, Pfizer, Roche, and Seagen; consulting fees from Apogepha, Astellas, AstraZeneca, Bristol Myers Squibb, Eisai, Ipsen, Janssen, Merck Serono, MSD, Pfizer, and Roche; payment or honoraria to him and his institution for lectures, presentations, speaker's bureaus, manuscript writing or educational events from Astellas, Bristol Myers Squibb, Ipsen, Merck Serono, MSD, Pfizer, Roche, and Seagen; support for attending meetings and/or travel from Ipsen and Merck & Co, Inc; payments to his institution for participation on a steering committee of Bristol Myers Squibb, MSD, and Seagen and participation on a data safety monitoring board or advisory board of MSD and Pfizer, outside the submitted work. K. Imai, B. Homet Moreno, and J. Z. Xu are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, NJ, USA, and have stock in Merck & Co, Inc, Rahway, NJ, USA. A. Alva reports funding to his institution for the present manuscript from MSD and research grants or contracts to his institution from MSD. T. Powles reports grants or contracts from Astellas, AstraZeneca, Bristol Myers Squibb, Eisai, Exelixis, Gilead, Ipsen, Johnson & Johnson, Merck Serono, MSD, Novartis, Pfizer, Seattle Genetics, and Roche; consulting fees from Astellas, AstraZeneca, Bristol Myers Squibb, Eisai, Exelixis, Incyte, Ipsen, Johnson & Johnson, Mashup, Merck Serono, MSD, Novartis, Pfizer, Roche, and Seattle Genetics; and payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing or educational events from Astellas, AstraZeneca, Bristol Myers Squibb, Eisai, Exelixis, Incyte, Ipsen, Johnson & Johnson, Mashup, Merck Serono, MSD, Novartis, Pfizer, Roche, and Seattle Genetics; support for attending meetings and/or travel from Astellas, AstraZeneca, Gilead, Ipsen, MSD, Pfizer, and Roche; participation on a data safety monitoring board or advisory board of Astellas, AstraZeneca, Bristol Myers Squibb, Eisai, Exelixis, Ipsen, Johnson & Johnson, Merck Serono, MSD, Novartis, Pfizer, Roche, and Seattle Genetics; and other financial or nonfinancial interests as principal investigator for AstraZeneca, Eisai, MSD, Novartis, Pfizer, and Roche/Genentech, outside the submitted work. H. J. Lee, A. Sella, and Y.-H. Chang declare no competing interests.
(Copyright © 2024. Published by Elsevier Inc.)