• Caicun Zhou, Benjamin Solomon, Herbert H Loong, Keunchil Park, Maurice Pérol, Edurne Arriola, Silvia Novello, Baohui Han, Jianying Zhou, Andrea Ardizzoni, M Perez Mak, Fernando C Santini, Yasir Y Elamin, Alexander Drilon, Jürgen Wolf, Nalin Payakachat, Minji K Uh, Deborah Rajakumar, Hongmei Han, Tarun Puri, Victoria Soldatenkova, A Bence Lin, Boris K Lin, Koichi Goto, and LIBRETTO-431 Trial Investigators.
• From Shanghai Pulmonary Hospital, Tongji University School of Medicine (C.Z.), and the Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University (B.H.), Shanghai, the Chinese University of Hong Kong, Hong Kong (H.H.L.), and the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou (J.Z.) - all in China; Peter MacCallum Cancer Institute, Melbourne, VIC, Australia (B.S.); Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea (K.P.); Centre Léon Bérard, Lyon, France (M.P.); Hospital del Mar, Barcelona (E.A.); the Department of Oncology, Azienda Ospedaliero-Universitaria San Luigi-Orbassano, University of Turin, Turin (S.N.), and IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna (A.A.) - both in Italy; Instituto do Câncer do Estado de São Paulo, University of São Paulo Medical School and Instituto D'Or de Ensino e Pesquisa (M.P.M.), and the Oncology Center, Hospital Śırio Libanês (F.C.S.) - both in São Paulo; the University of Texas M.D. Anderson Cancer Center, Houston (Y.Y.E.); Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (A.D.); the Center for Integrated Oncology, University Hospital of Cologne, Cologne, Germany (J.W.); Loxo@Lilly (H.H.) and Eli Lilly (N.P., M.K.U., D.R., T.P., V.S., A.B.L., B.K.L.) - both in Indianapolis; and National Cancer Center Hospital East, Kashiwa, Japan (K.G.).
• N. Engl. J. Med. 2023 Nov 16; 389 (20): 183918501839-1850.

BackgroundSelpercatinib, a highly selective potent and brain-penetrant RET inhibitor, was shown to have efficacy in patients with advanced RET fusion-positive non-small-cell lung cancer (NSCLC) in a nonrandomized phase 1-2 study.MethodsIn a randomized phase 3 trial, we evaluated the efficacy and safety of first-line selpercatinib as compared with control treatment that consisted of platinum-based chemotherapy with or without pembrolizumab at the investigator's discretion. The primary end point was progression-free survival assessed by blinded independent central review in both the intention-to-treat-pembrolizumab population (i.e., patients whose physicians had planned to treat them with pembrolizumab in the event that they were assigned to the control group) and the overall intention-to-treat population. Crossover from the control group to the selpercatinib group was allowed if disease progression as assessed by blinded independent central review occurred during receipt of control treatment.ResultsIn total, 212 patients underwent randomization in the intention-to-treat-pembrolizumab population. At the time of the preplanned interim efficacy analysis, median progression-free survival was 24.8 months (95% confidence interval [CI], 16.9 to not estimable) with selpercatinib and 11.2 months (95% CI, 8.8 to 16.8) with control treatment (hazard ratio for progression or death, 0.46; 95% CI, 0.31 to 0.70; P<0.001). The percentage of patients with an objective response was 84% (95% CI, 76 to 90) with selpercatinib and 65% (95% CI, 54 to 75) with control treatment. The cause-specific hazard ratio for the time to progression affecting the central nervous system was 0.28 (95% CI, 0.12 to 0.68). Efficacy results in the overall intention-to-treat population (261 patients) were similar to those in the intention-to-treat-pembrolizumab population. The adverse events that occurred with selpercatinib and control treatment were consistent with those previously reported.ConclusionsTreatment with selpercatinib led to significantly longer progression-free survival than platinum-based chemotherapy with or without pembrolizumab among patients with advanced RET fusion-positive NSCLC. (Funded by Eli Lilly and others; ClinicalTrials.gov number, NCT04194944.).Copyright © 2023 Massachusetts Medical Society.

27 keywords...

hide…