Presenting Author: Steven L. McCune, MD, PhD, Wellstar Northwest Georgia Oncology Centers, Marietta, GA
Co-Authors: David P. Carbone, The Ohio State University Comprehensive Cancer Center, Columbus, OH; Tudor-Eliade Ciuleanu, Institutul Oncologic Prof Dr Ion Chiricută and University of Medicine and Pharmacy Iuliu Haţieganu, Cluj-Napoca, Romania; Michael Schenker, SF Nectarie Oncology Center, Craiova, Romania; Manuel Cobo-Dols, Unidad de Gestión Clínica Intercentros de Oncología Médica, Hospitales Universitarios Regional y Virgen de la Victoria, IBIMA, Málaga, Spain; Stephanie Bordenave, L’institut du Thorax, Nantes, France; Oscar Juan-Vidal, Hospital Universitario La Fe, Valencia, Spain; Juliana Menezes, Hospital Nossa Senhora da Conceição, Porto Alegre, Brazil; Niels Reinmuth, Asklepios Lung Clinic, Munich-Gauting, Germany; Eduardo Richardet, IONC Instituto Oncológico de Córdoba, Cordoba, Argentina; Ying Cheng, Jilin Cancer Hospital, Changchun, Jilin, China; Hideaki Mizutani, Saitama Cancer Center, Saitama, Japan; Luis G. Paz-Ares, Hospital Universitario, 12 de Octubre, Universidad Complutense de Madrid, Madrid, Spain; Shun Lu, Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai JiaoTong University, Shanghai, China; Thomas John, Austin Hospital, Heidelberg, Victoria, Australia; Xiaoqing Zhang, Nan Hu, David Balli, Vipul Baxi, and Jaclyn Neely, Bristol Myers Squibb, Princeton, NJ; Martin Reck, Airway Research Center North, German Center for Lung Research, LungClinic, Grosshansdorf, Germany
BACKGROUND: In CheckMate 9LA (NCT03215706), first-line nivolumab + ipilimumab + chemotherapy (N+I+C) demonstrated durable survival benefit in patients with metastatic non–small cell lung cancer (NSCLC) versus chemotherapy alone.
OBJECTIVE: To report updated efficacy and safety with a 4-year minimum follow-up.
METHODS: Adults with stage IV/recurrent NSCLC (no known sensitizing EGFR/ALK alterations) and Eastern Cooperative Oncology Group performance score ≤1 were randomized 1:1 to nivolumab 360 mg every 3 weeks plus ipilimumab 1 mg/kg every 6 weeks and 2 cycles of chemotherapy (n=361) or 4 cycles of chemotherapy alone (n=358). Patients were stratified by sex, tumor PD-L1 (<1% vs ≥1%), and histology (squamous vs nonsquamous). Maintenance pemetrexed was allowed in the chemotherapy arm (nonsquamous NSCLC). Assessments included overall survival (OS), progression-free survival, objective response rate, safety, and treatment-free interval (TFI; time from last study dose to start of first subsequent systemic treatment or death).
RESULTS: At 47.9 months of minimum follow-up (database lock, February 2023; median follow-up, 54.5 months), N+I+C continued to provide long-term, durable OS benefit versus chemotherapy in all randomized patients (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.63-0.87; 4-year OS rate, 21% vs 16%, respectively). Similar clinical benefit was seen with N+I+C versus chemotherapy by PD-L1 status (PD-L1 <1%: HR, 0.66; 95% CI, 0.50-0.86; 4-year OS rate 23% vs 13%, respectively; PD-L1 ≥1%: HR, 0.74; 95% CI, 0.60-0.92; 4-year OS rate 21% vs 16%, respectively) and by histology (squamous: HR, 0.64; 95% CI, 0.48-0.84; 4-year OS rate 20% vs 10%, respectively; nonsquamous: HR, 0.80; 95% CI, 0.66-0.97; 4-year OS rate 22% vs 19%, respectively). The proportions of responders with ongoing response at 4 years were 25% versus 12% (all randomized), 29% versus 0% (PD-L1 <1%), 24% versus 15% (PD-L1 ≥1%), 17% versus 6% (squamous), and 30% versus 16% (nonsquamous). In all patients who received N+I+C (n=358), the median TFI was 2.2 months, and 11% of the patients remained treatment-free and alive at 4 years. In patients who discontinued all components of N+I+C as a result of treatment-related adverse events (n=61), the 4-year OS rate was 41%, the median TFI was 10.6 months, and the 4-year TFI rate was 27%. No new safety signals were identified with longer follow-up.
CONCLUSION: With a 4-year minimum follow-up, patients who received N+I+C continued to derive long-term, durable efficacy benefit versus chemotherapy, regardless of PD-L1 expression or histology, with greater magnitude of benefit in patients with PD-L1 <1% or squamous histology. Together, these data further reinforce the use of N+I+C as an efficacious first-line treatment option for patients with metastatic NSCLC.
This abstract was previously presented at the 2023 American Society of Clinical Oncology Annual Meeting.