TY - JOUR
TI - Nivolumab plus Ipilimumab in Advanced Non-Small-Cell Lung Cancer.
AU - Hellmann, Matthew D.
AU - Paz-Ares, Luis
AU - Bernabe Caro, Reyes
AU - Zurawski, Bogdan
AU - Kim, Sang-We
AU - Carcereny Costa, Enric
AU - Park, Keunchil
AU - Alexandru, Aurelia
AU - Lupinacci, Lorena
AU - de la Mora Jimenez, Emmanuel
AU - Sakai, Hiroshi
AU - Albert, Istvan
AU - Vergnenegre, Alain
AU - Peters, Solange
AU - Syrigos, Konstantinos
AU - Barlesi, Fabrice
AU - Reck, Martin
AU - Borghaei, Hossein
AU - Brahmer, Julie R.
AU - O'Byrne, Kenneth J.
AU - Geese, William J.
AU - Bhagavatheeswaran, Prabhu
AU - Rabindran, Sridhar K.
AU - Kasinathan, Ravi S.
AU - Nathan, Faith E.
AU - Ramalingam, Suresh S.
JO - The New England journal of medicine
PY - 2019
VL - 381
TODO - 21
SP - 2020--2031
PB - 
SN - null
TODO - 10.1056/NEJMoa1910231
TODO - Humans, Female, Male, Adult, Survival Analysis, Aged, Middle Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use, Antineoplastic Agents, Immunological/*administration & dosage/adverse effects, Ipilimumab/*administration & dosage/adverse effects, Nivolumab/*administration & dosage/adverse effects, B7-H1 Antigen/metabolism, Carcinoma, Non-Small-Cell Lung/*drug therapy/metabolism/mortality, Lung Neoplasms/*drug therapy/metabolism/mortality
TODO - 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.).
ER -