Hellmann, Matthew, Paz-Ares, Luis, Bernabe Caro, Reyes, Zurawski, Bogdan, Kim, Sang-We, Carcereny Costa, Enric, Park, Keunchil, Alexandru, Aurelia, Lupinacci, Lorena, de La Mora Jimenez, Emmanuel, Sakai, Hiroshi, Albert, Istvan, Vergnenègre, Alain, Peters, Solange, Syrigos, Konstantinos, Barlesi, Fabrice, Reck, Martin, Borghaei, Hossein, Brahmer, Julie, O'Byrne, Kenneth, Geese, William, Bhagavatheeswaran, Prabhu, Rabindran, Sridhar, Kasinathan, Ravi, Nathan, Faith, Ramalingam, Suresh, O’byrne, Kenneth, Samsung Medical Center Sungkyunkwan University School of Medicine, Institute Division of Hematology/Oncology, Bioinformatics Consulting Center, Pennsylvania State University (Penn State), Penn State System-Penn State System, Service de Pathologie respiratoire et allergologie [CHU Limoges], CHU Limoges, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), National and Kapodistrian University of Athens (NKUA), Assistance Publique - Hôpitaux de Marseille (APHM), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), AstraZeneca, Bristol-Myers Squibb, and Ono Pharmaceutical
[Background] In an early-phase study involving patients with advanced non–small-cell lung cancer (NSCLC), the response rate was better with nivolumab plus ipilimumab than with nivolumab monotherapy, particularly among patients with tumors that expressed programmed death ligand 1 (PD-L1). Data are needed to assess the long-term benefit of nivolumab plus ipilimumab in patients with NSCLC., [Methods] In this open-label, phase 3 trial, we randomly assigned patients with stage IV or recurrent NSCLC and a PD-L1 expression level of 1% or more in a 1:1:1 ratio to receive nivolumab plus ipilimumab, nivolumab alone, or chemotherapy. The patients who had a PD-L1 expression level of less than 1% were randomly assigned in a 1:1:1 ratio to receive nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy alone. All the patients had received no previous chemotherapy. The primary end point reported here was overall survival with nivolumab plus ipilimumab as compared with chemotherapy in patients with a PD-L1 expression level of 1% or more., [Results] Among the patients with a PD-L1 expression level of 1% or more, the median duration of overall survival was 17.1 months (95% confidence interval [CI], 15.0 to 20.1) with nivolumab plus ipilimumab and 14.9 months (95% CI, 12.7 to 16.7) with chemotherapy (P=0.007), with 2-year overall survival rates of 40.0% and 32.8%, respectively. The median duration of response was 23.2 months with nivolumab plus ipilimumab and 6.2 months with chemotherapy. The overall survival benefit was also observed in patients with a PD-L1 expression level of less than 1%, with a median duration of 17.2 months (95% CI, 12.8 to 22.0) with nivolumab plus ipilimumab and 12.2 months (95% CI, 9.2 to 14.3) with chemotherapy. Among all the patients in the trial, the median duration of overall survival was 17.1 months (95% CI, 15.2 to 19.9) with nivolumab plus ipilimumab and 13.9 months (95% CI, 12.2 to 15.1) with chemotherapy. The percentage of patients with grade 3 or 4 treatment-related adverse events in the overall population was 32.8% with nivolumab plus ipilimumab and 36.0% with chemotherapy., [Conclusions] First-line treatment with nivolumab plus ipilimumab resulted in a longer duration of overall survival than did chemotherapy in patients with NSCLC, independent of the PD-L1 expression level. No new safety concerns emerged with longer follow-up. (Funded by Bristol-Myers Squibb and Ono Pharmaceutical; CheckMate 227 ClinicalTrials.gov number, NCT02477826. opens in new tab.), Funded by Bristol-Myers Squibb and Ono Pharmaceutical.