• Robert J Motzer, Konstantin Penkov, John Haanen, Brian Rini, Laurence Albiges, Matthew T Campbell, Balaji Venugopal, Christian Kollmannsberger, Sylvie Negrier, Motohide Uemura, Jae L Lee, Aleksandr Vasiliev, Wilson H Miller, Howard Gurney, Manuela Schmidinger, James Larkin, Michael B Atkins, Jens Bedke, Boris Alekseev, Jing Wang, Mariangela Mariani, Paul B Robbins, Aleksander Chudnovsky, Camilla Fowst, Subramanian Hariharan, Bo Huang, Alessandra di Pietro, and Toni K Choueiri.
• From Memorial Sloan Kettering Cancer Center (R.J.M.) and Pfizer (S.H.), New York; Private Medical Institution Euromedservice (K.P.) and Nonstate Health Institution Road Clinical Hospital-Russian Railways (A.V.), St. Petersburg, and the Moscow Scientific Research Oncology Institute, Moscow (B.A.) - all in Russia; the Netherlands Cancer Institute, Amsterdam (J.H.); the Cleveland Clinic, Cleveland (B.R.); Institut Gustave Roussy, Villejuif (L.A.), and Centre Léon Bérard, University of Lyon, Lyon (S.N.) - both in France; the University of Texas M.D. Anderson Cancer Center, Houston (M.T.C.); University of Glasgow, Beatson West of Scotland Cancer Centre, Glasgow (B.V.), and Royal Marsden NHS Foundation Trust, London (J.L.) - both in the United Kingdom; British Columbia Cancer Agency, Vancouver (C.K.), and Lady Davis Institute and Jewish General Hospital, McGill University, Montreal (W.H.M.) - both in Canada; Osaka University Hospital, Osaka, Japan (M.U.); University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea (J.L.L.); Macquarie University, Sydney (H.G.); Department of Medicine I, Clinical Division of Oncology and Comprehensive Cancer Center, Medical University of Vienna, Vienna (M.S.); Georgetown Lombardi Comprehensive Cancer Center, Washington, DC (M.B.A.); Department of Urology, University of Tübingen, Tübingen, Germany (J.B.); Pfizer, Cambridge (J.W., A.C.), and the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute, and Brigham and Women's Hospital, Boston (T.K.C.) - both in Massachusetts; Pfizer (M.M., A.P.) and Pfizer Italia (C.F.), Milan; Pfizer, San Diego, CA (P.B.R.); and Pfizer, Groton, CT (B.H.).
• N. Engl. J. Med. 2019 Mar 21; 380 (12): 1103-1115.

BackgroundIn a single-group, phase 1b trial, avelumab plus axitinib resulted in objective responses in patients with advanced renal-cell carcinoma. This phase 3 trial involving previously untreated patients with advanced renal-cell carcinoma compared avelumab plus axitinib with the standard-of-care sunitinib.MethodsWe randomly assigned patients in a 1:1 ratio to receive avelumab (10 mg per kilogram of body weight) intravenously every 2 weeks plus axitinib (5 mg) orally twice daily or sunitinib (50 mg) orally once daily for 4 weeks (6-week cycle). The two independent primary end points were progression-free survival and overall survival among patients with programmed death ligand 1 (PD-L1)-positive tumors. A key secondary end point was progression-free survival in the overall population; other end points included objective response and safety.ResultsA total of 886 patients were assigned to receive avelumab plus axitinib (442 patients) or sunitinib (444 patients). Among the 560 patients with PD-L1-positive tumors (63.2%), the median progression-free survival was 13.8 months with avelumab plus axitinib, as compared with 7.2 months with sunitinib (hazard ratio for disease progression or death, 0.61; 95% confidence interval [CI], 0.47 to 0.79; P<0.001); in the overall population, the median progression-free survival was 13.8 months, as compared with 8.4 months (hazard ratio, 0.69; 95% CI, 0.56 to 0.84; P<0.001). Among the patients with PD-L1-positive tumors, the objective response rate was 55.2% with avelumab plus axitinib and 25.5% with sunitinib; at a median follow-up for overall survival of 11.6 months and 10.7 months in the two groups, 37 patients and 44 patients had died, respectively. Adverse events during treatment occurred in 99.5% of patients in the avelumab-plus-axitinib group and in 99.3% of patients in the sunitinib group; these events were grade 3 or higher in 71.2% and 71.5% of the patients in the respective groups.ConclusionsProgression-free survival was significantly longer with avelumab plus axitinib than with sunitinib among patients who received these agents as first-line treatment for advanced renal-cell carcinoma. (Funded by Pfizer and Merck [Darmstadt, Germany]; JAVELIN Renal 101 ClinicalTrials.gov number, NCT02684006.).Copyright © 2019 Massachusetts Medical Society.

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