Toni K Choueiri1, Piotr Tomczak1, Se Hoon Park1, Balaji Venugopal1, Thomas Ferguson1, Yen-Hwa Chang1, Jaroslav Hajek1, Stefan N Symeonides1, Jae Lyun Lee1, Naveed Sarwar1, Antoine Thiery-Vuillemin1, Marine Gross-Goupil1, Mauricio Mahave1, Naomi B Haas1, Piotr Sawrycki1, Howard Gurney1, Christine Chevreau1, Bohuslav Melichar1, Evgeniy Kopyltsov1, Ajjai Alva1, John M Burke1, Gurjyot Doshi1, Delphine Topart1, Stephane Oudard1, Hans Hammers1, Hiroshi Kitamura1, Jens Bedke1, Rodolfo F Perini1, Pingye Zhang1, Kentaro Imai1, Jaqueline Willemann-Rogerio1, David I Quinn1, Thomas Powles1. 1. From Dana-Farber Cancer Institute, Boston (T.K.C.); Poznan University of Medical Sciences, Poznan (P.T.), and Wojewódzki Szpital Zespolony im. L. Rydygiera w Toruniu, Torun (P.S.) - both in Poland; Sungkyunkwan University, Samsung Medical Center (S.H.P.), and Asan Medical Center, University of Ulsan College of Medicine (J.L.L.) - both in Seoul, South Korea; Beatson West of Scotland Cancer Centre and University of Glasgow, Glasgow (B.V.), Edinburgh Cancer Centre and University of Edinburgh, Edinburgh (S.N.S.), and Imperial College Healthcare NHS Trust (N.S.) and the Royal Free Hospital NHS Trust, University College London (T.P.), London - all in the United Kingdom; Fiona Stanley Hospital, Perth, WA (T.F.), and Macquarie University, Sydney (H.G.) - both in Australia; Taipei Veterans General Hospital, Taipei, Taiwan (Y.-H.C.); Fakultni Nemocnice Ostrava, Ostrava (J.H.), and Palacký University and University Hospital Olomouc, Olomouc (B.M.) - both in the Czech Republic; University Hospital Jean Minjoz, Besançon (A.T.-V.), University Hospital Bordeaux-Hôpital Saint-André, Bordeaux (M.G.-G.), Institut Universitaire du Cancer Toulouse-Oncopole, Toulouse (C.C.), Centre Hospitalier Universitaire de Montpellier, Montpellier (D.T.), and Hôpital Européen Georges Pompidou, University of Paris, Paris (S.O.) - all in France; Fundación Arturo López Pérez, Santiago, Chile (M.M.); Abramson Cancer Center, Philadelphia (N.H.); Omsk Clinical Oncology Dispensary, Omsk, Russia (E.K.); the University of Michigan, Ann Arbor (A.A.); Rocky Mountain Cancer Centers and U.S. Oncology Research, Denver (J.M.B.); Texas Oncology, U.S. Oncology Research, Woodlands (G.D.), and the University of Texas Southwestern, Dallas (H.H.); the University of Toyama, Toyama, Japan (H.K.); Eberhard Karls University Tübingen, Tübingen, Germany (J.B.); Merck, Kenilworth, NJ (R.F.P., P.Z., K.I., J.W.-R.); and USC Norris Comprehensive Cancer Center, Los Angeles (D.I.Q.).
Abstract
BACKGROUND: Patients with renal-cell carcinoma who undergo nephrectomy have no options for adjuvant therapy to reduce the risk of recurrence that have high levels of supporting evidence. METHODS: In a double-blind, phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with clear-cell renal-cell carcinoma who were at high risk for recurrence after nephrectomy, with or without metastasectomy, to receive either adjuvant pembrolizumab (at a dose of 200 mg) or placebo intravenously once every 3 weeks for up to 17 cycles (approximately 1 year). The primary end point was disease-free survival according to the investigator's assessment. Overall survival was a key secondary end point. Safety was a secondary end point. RESULTS: A total of 496 patients were randomly assigned to receive pembrolizumab, and 498 to receive placebo. At the prespecified interim analysis, the median time from randomization to the data-cutoff date was 24.1 months. Pembrolizumab therapy was associated with significantly longer disease-free survival than placebo (disease-free survival at 24 months, 77.3% vs. 68.1%; hazard ratio for recurrence or death, 0.68; 95% confidence interval [CI], 0.53 to 0.87; P = 0.002 [two-sided]). The estimated percentage of patients who remained alive at 24 months was 96.6% in the pembrolizumab group and 93.5% in the placebo group (hazard ratio for death, 0.54; 95% CI, 0.30 to 0.96). Grade 3 or higher adverse events of any cause occurred in 32.4% of the patients who received pembrolizumab and in 17.7% of those who received placebo. No deaths related to pembrolizumab therapy occurred. CONCLUSIONS: Pembrolizumab treatment led to a significant improvement in disease-free survival as compared with placebo after surgery among patients with kidney cancer who were at high risk for recurrence. (Funded by Merck Sharp and Dohme, a subsidiary of Merck; KEYNOTE-564 ClinicalTrials.gov number, NCT03142334.).
BACKGROUND: Patients with renal-cell carcinoma who undergo nephrectomy have no options for adjuvant therapy to reduce the risk of recurrence that have high levels of supporting evidence. METHODS: In a double-blind, phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with clear-cell renal-cell carcinoma who were at high risk for recurrence after nephrectomy, with or without metastasectomy, to receive either adjuvant pembrolizumab (at a dose of 200 mg) or placebo intravenously once every 3 weeks for up to 17 cycles (approximately 1 year). The primary end point was disease-free survival according to the investigator's assessment. Overall survival was a key secondary end point. Safety was a secondary end point. RESULTS: A total of 496 patients were randomly assigned to receive pembrolizumab, and 498 to receive placebo. At the prespecified interim analysis, the median time from randomization to the data-cutoff date was 24.1 months. Pembrolizumab therapy was associated with significantly longer disease-free survival than placebo (disease-free survival at 24 months, 77.3% vs. 68.1%; hazard ratio for recurrence or death, 0.68; 95% confidence interval [CI], 0.53 to 0.87; P = 0.002 [two-sided]). The estimated percentage of patients who remained alive at 24 months was 96.6% in the pembrolizumab group and 93.5% in the placebo group (hazard ratio for death, 0.54; 95% CI, 0.30 to 0.96). Grade 3 or higher adverse events of any cause occurred in 32.4% of the patients who received pembrolizumab and in 17.7% of those who received placebo. No deaths related to pembrolizumab therapy occurred. CONCLUSIONS: Pembrolizumab treatment led to a significant improvement in disease-free survival as compared with placebo after surgery among patients with kidney cancer who were at high risk for recurrence. (Funded by Merck Sharp and Dohme, a subsidiary of Merck; KEYNOTE-564 ClinicalTrials.gov number, NCT03142334.).
Authors: Lewis Au; Emine Hatipoglu; Marc Robert de Massy; Kevin Litchfield; Gordon Beattie; Andrew Rowan; Desiree Schnidrig; Rachael Thompson; Fiona Byrne; Stuart Horswell; Nicos Fotiadis; Steve Hazell; David Nicol; Scott T C Shepherd; Annika Fendler; Robert Mason; Lyra Del Rosario; Kim Edmonds; Karla Lingard; Sarah Sarker; Mary Mangwende; Eleanor Carlyle; Jan Attig; Kroopa Joshi; Imran Uddin; Pablo D Becker; Mariana Werner Sunderland; Ayse Akarca; Ignazio Puccio; William W Yang; Tom Lund; Kim Dhillon; Marcos Duran Vasquez; Ehsan Ghorani; Hang Xu; Charlotte Spencer; José I López; Anna Green; Ula Mahadeva; Elaine Borg; Miriam Mitchison; David A Moore; Ian Proctor; Mary Falzon; Lisa Pickering; Andrew J S Furness; James L Reading; Roberto Salgado; Teresa Marafioti; Mariam Jamal-Hanjani; George Kassiotis; Benny Chain; James Larkin; Charles Swanton; Sergio A Quezada; Samra Turajlic Journal: Cancer Cell Date: 2021-10-28 Impact factor: 31.743
Authors: Giuseppe Fallara; Alessandro Larcher; Giuseppe Rosiello; Daniele Raggi; Laura Marandino; Alberto Martini; Giuseppe Basile; Gianmarco Colandrea; Daniele Cignoli; Federico Belladelli; Chiara Re; Giacomo Musso; Francesco Cei; Roberto Bertini; Alberto Briganti; Andrea Salonia; Francesco Montorsi; Andrea Necchi; Umberto Capitanio Journal: World J Urol Date: 2022-09-20 Impact factor: 3.661