• Leora Horn, Aaron S Mansfield, Aleksandra Szczęsna, Libor Havel, Maciej Krzakowski, Maximilian J Hochmair, Florian Huemer, György Losonczy, Melissa L Johnson, Makoto Nishio, Martin Reck, Tony Mok, Sivuonthanh Lam, David S Shames, Juan Liu, Beiying Ding, Ariel Lopez-Chavez, Fairooz Kabbinavar, Wei Lin, Alan Sandler, Stephen V Liu, and IMpower133 Study Group.
• From Vanderbilt University Medical Center (L. Horn) and Sarah Cannon Research Institute-Tennessee Oncology (M.L.J.), Nashville; Mayo Clinic, Rochester, MN (A.S.M.); Mazowieckie Centrum Leczenia Chorób Płuc i Gruźlicy, Otwock (A. Szczęsna), and Centrum Onkologii-Instytut im. Marii Skłodowskiej-Curie w Warszawie, Warsaw (M.K.) - both in Poland; Thomayerova Nemocnice, Pneumologická Klinika 1.LF UK, Prague, Czech Republic (L. Havel); the Department of Respiratory and Critical Care Medicine (M.J.H.) and the 2nd Department of Respiratory and Critical Care Medicine (F.H.), Ludwig Boltzmann Institute for COPD and Respiratory Epidemiology-Sozialmedizinisches Zentrum Baumgartner Höhe, Otto-Wagner-Spital, Vienna; Semmelweis Egyetem ÁOK, Pulmonológiai Klinika, Budapest, Hungary (G.L.); the Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo (M.N.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); State Key Laboratory of South China, Chinese University of Hong Kong, Hong Kong (T.M.), and F. Hoffmann-La Roche, Shanghai (J.L.) - both in China; Genentech, South San Francisco, CA (S.L., D.S.S., B.D., A.L.-C., F.K., W.L., A. Sandler); and Georgetown University, Washington DC (S.V.L.).
• N. Engl. J. Med. 2018 Dec 6; 379 (23): 2220-2229.

BackgroundEnhancing tumor-specific T-cell immunity by inhibiting programmed death ligand 1 (PD-L1)-programmed death 1 (PD-1) signaling has shown promise in the treatment of extensive-stage small-cell lung cancer. Combining checkpoint inhibition with cytotoxic chemotherapy may have a synergistic effect and improve efficacy.MethodsWe conducted this double-blind, placebo-controlled, phase 3 trial to evaluate atezolizumab plus carboplatin and etoposide in patients with extensive-stage small-cell lung cancer who had not previously received treatment. Patients were randomly assigned in a 1:1 ratio to receive carboplatin and etoposide with either atezolizumab or placebo for four 21-day cycles (induction phase), followed by a maintenance phase during which they received either atezolizumab or placebo (according to the previous random assignment) until they had unacceptable toxic effects, disease progression according to Response Evaluation Criteria in Solid Tumors, version 1.1, or no additional clinical benefit. The two primary end points were investigator-assessed progression-free survival and overall survival in the intention-to-treat population.ResultsA total of 201 patients were randomly assigned to the atezolizumab group, and 202 patients to the placebo group. At a median follow-up of 13.9 months, the median overall survival was 12.3 months in the atezolizumab group and 10.3 months in the placebo group (hazard ratio for death, 0.70; 95% confidence interval [CI], 0.54 to 0.91; P=0.007). The median progression-free survival was 5.2 months and 4.3 months, respectively (hazard ratio for disease progression or death, 0.77; 95% CI, 0.62 to 0.96; P=0.02). The safety profile of atezolizumab plus carboplatin and etoposide was consistent with the previously reported safety profile of the individual agents, with no new findings observed.ConclusionsThe addition of atezolizumab to chemotherapy in the first-line treatment of extensive-stage small-cell lung cancer resulted in significantly longer overall survival and progression-free survival than chemotherapy alone. (Funded by F. Hoffmann-La Roche/Genentech; IMpower133 ClinicalTrials.gov number, NCT02763579 .).

26 keywords...

hide…