1. Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma
- Author
-
David I. Quinn, Toni K. Choueiri, Stéphane Culine, Joaquim Bellmunt, Daniel P. Petrylak, Howard Gurney, Nicholas J. Vogelzang, Dean F. Bajorin, Ronald de Wit, Christian Heinrich Poehlein, Yabing Mai, Miguel Angel Climent, Lawrence Fong, David J. Vaughn, Andrea Necchi, Yves Fradet, Cora N. Sternberg, Jae-Lyun Lee, Rodolfo F. Perini, Winald R. Gerritsen, Medical Oncology, Bellmunt, J, de Wit, R, Vaughn, Dj, Fradet, Y, Lee, Jl, Fong, L, Vogelzang, Nj, Climent, Ma, Petrylak, Dp, Choueiri, Tk, Necchi, A, Gerritsen, W, Gurney, H, Quinn, Di, Culine, S, Sternberg, Cn, Mai, Y, Poehlein, Ch, Perini, Rf, and Bajorin, Df
- Subjects
0301 basic medicine ,Oncology ,medicine.medical_specialty ,Metastatic Urothelial Carcinoma ,medicine.medical_treatment ,Pembrolizumab ,Avelumab ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,medicine ,Survival analysis ,Chemotherapy ,Vinflunine ,business.industry ,Uretra -- Càncer -- Tractament ,General Medicine ,Vinblastine ,030104 developmental biology ,chemistry ,Docetaxel ,Urological cancers Radboud Institute for Health Sciences [Radboudumc 15] ,030220 oncology & carcinogenesis ,Càncer -- Tractament ,business ,medicine.drug - Abstract
Contains fulltext : 170338.pdf (Publisher’s version ) (Open Access) Background Patients with advanced urothelial carcinoma that progresses after platinum-based chemotherapy have a poor prognosis and limited treatment options. Methods In this open-label, international, phase 3 trial, we randomly assigned 542 patients with advanced urothelial cancer that recurred or progressed after platinum-based chemotherapy to receive pembrolizumab (a highly selective, humanized monoclonal IgG4kappa isotype antibody against programmed death 1 [PD-1]) at a dose of 200 mg every 3 weeks or the investigator's choice of chemotherapy with paclitaxel, docetaxel, or vinflunine. The coprimary end points were overall survival and progression-free survival, which were assessed among all patients and among patients who had a tumor PD-1 ligand (PD-L1) combined positive score (the percentage of PD-L1-expressing tumor and infiltrating immune cells relative to the total number of tumor cells) of 10% or more. Results The median overall survival in the total population was 10.3 months (95% confidence interval [CI], 8.0 to 11.8) in the pembrolizumab group, as compared with 7.4 months (95% CI, 6.1 to 8.3) in the chemotherapy group (hazard ratio for death, 0.73; 95% CI, 0.59 to 0.91; P=0.002). The median overall survival among patients who had a tumor PD-L1 combined positive score of 10% or more was 8.0 months (95% CI, 5.0 to 12.3) in the pembrolizumab group, as compared with 5.2 months (95% CI, 4.0 to 7.4) in the chemotherapy group (hazard ratio, 0.57; 95% CI, 0.37 to 0.88; P=0.005). There was no significant between-group difference in the duration of progression-free survival in the total population (hazard ratio for death or disease progression, 0.98; 95% CI, 0.81 to 1.19; P=0.42) or among patients who had a tumor PD-L1 combined positive score of 10% or more (hazard ratio, 0.89; 95% CI, 0.61 to 1.28; P=0.24). Fewer treatment-related adverse events of any grade were reported in the pembrolizumab group than in the chemotherapy group (60.9% vs. 90.2%); there were also fewer events of grade 3, 4, or 5 severity reported in the pembrolizumab group than in the chemotherapy group (15.0% vs. 49.4%). Conclusions Pembrolizumab was associated with significantly longer overall survival (by approximately 3 months) and with a lower rate of treatment-related adverse events than chemotherapy as second-line therapy for platinum-refractory advanced urothelial carcinoma. (Funded by Merck; KEYNOTE-045 ClinicalTrials.gov number, NCT02256436 .).
- Published
- 2017