Randomized phase III KEYNOTE-045 trial of pembrolizumab versus paclitaxel,docetaxel, or vinflunine in recurrent advanced urothelial cancer: results of >2 years of follow-up |
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| Institution: | 1. Department of Surgery/Urology, CHU de Québec-Université Laval, Québec City, Canada;2. Department of Medical Oncology, PSMAR-IMIM Research Institute, Barcelona, Spain and Harvard Medical School University, Boston, USA;3. Department of Medical Oncology, Abramson Cancer Center, Perelman Center for Advanced Medicine, Philadelphia, USA;4. Department of Oncology, Asan Medical Center and University of Ulsan College of Medicine, Seoul, Republic of Korea;5. Department of Medicine and Urology, University of California San Francisco, San Francisco;6. Department of Medical Oncology, Comprehensive Cancer Centers of Nevada, Las Vegas, USA;7. Department of Medical Oncology, Fundación Instituto Valenciano de Oncología, Valencia, Spain;8. Division of Medical Oncology, Smilow Cancer Hospital at Yale University, New Haven;9. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA;10. Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy;11. Department of Medical Oncology, Radboud University Medical Center, Nijmegen, The Netherlands;12. Department of Medical Oncology, Westmead Hospital and Macquarie University, Sydney, NSW, Australia;13. Department of Medical Oncology, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, USA;14. Department of Medical Oncology, Hôpital Saint-Louis, Paris, France;15. Department of Medical Oncology, Englander Institute for Precision Medicine, Weill Cornell Medicine, New York-Presbyterian, New York;16. Department of Medical Oncology, Merck & Co., Inc., Kenilworth, USA;17. Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands;18. Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, USA |
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| Abstract: | BackgroundNovel second-line treatments are needed for patients with advanced urothelial cancer (UC). Interim analysis of the phase III KEYNOTE-045 study showed a superior overall survival (OS) benefit of pembrolizumab, a programmed death 1 inhibitor, versus chemotherapy in patients with advanced UC that progressed on platinum-based chemotherapy. Here we report the long-term safety and efficacy outcomes of KEYNOTE-045.Patients and methodsAdult patients with histologically/cytologically confirmed UC whose disease progressed after first-line, platinum-containing chemotherapy were enrolled. Patients were randomly assigned 1 : 1 to receive pembrolizumab 200 mg every 3 weeks (Q3W)] or investigator’s choice of paclitaxel (175 mg/m2 Q3W), docetaxel (75 mg/m2 Q3W), or vinflunine (320 mg/m2 Q3W). Primary end points were OS and progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) by blinded independent central radiology review (BICR). A key secondary end point was objective response rate per RECIST v1.1 by BICR.ResultsA total of 542 patients were enrolled (pembrolizumab, n = 270; chemotherapy, n = 272). Median follow-up as of 26 October 2017 was 27.7 months. Median 1- and 2-year OS rates were higher with pembrolizumab (44.2% and 26.9%, respectively) than chemotherapy (29.8% and 14.3%, respectively). PFS rates did not differ between treatment arms; however, 1- and 2-year PFS rates were higher with pembrolizumab. The objective response rate was also higher with pembrolizumab (21.1% versus 11.0%). Median duration of response to pembrolizumab was not reached (range 1.6+ to 30.0+ months) versus chemotherapy (4.4 months; range 1.4+ to 29.9+ months). Pembrolizumab had lower rates of any grade (62.0% versus 90.6%) and grade ≥3 (16.5% versus 50.2%) treatment-related adverse events than chemotherapy.ConclusionsLong-term results (>2 years’ follow-up) were consistent with those of previously reported analyses, demonstrating continued clinical benefit of pembrolizumab over chemotherapy for efficacy and safety for treatment of locally advanced/metastatic, platinum-refractory UC.Trial registrationClinicalTrials.gov: NCT02256436. |
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