Presenter: David P. Carbone, MD, PhD, The Ohio State University Comprehensive Cancer Center, Columbus, OH
Co-Authors: Tudor-Eliade Ciuleanu, MD, PhD, Institutul Oncologic Prof Dr Ion Chiricuta and University of Medicine and Pharmacy Iulia Hatieganu, Cluj-Napoca, Romania; Manuel Cobo-Dols, MD, Unidad de Gestión Clínica Intercentros de Oncología Médica, Hospitales Universitarios Regional y Virgen de la Victoria, Malaga, Spain; Michael Schenker, MD, SF Nectarie Oncology Center, Craiova, Romania; Bogdan Zurawski, MD, Ambulatorium Chemioterapii, Bydgoszcz, Poland; Juliana Menezes, MD, Hospital Nossa Senhora da Conceição, Porta Alegre, Brazil; Eduardo A. Richardet, MD, Instituto Oncológico de Córdoba, Córdoba, Argentina; Jaafar Bennouna, MD, University Hospital of Nantes and INSERM, CRCINA, Nantes, France; Ying Cheng, MD, Jilin Cancer Hospital, Changchun, China; Enriqueta Felip, MD, PhD, Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology, Barcelona, Spain; Oscar J. Juan-Vidal, MD, Hospital Universitario La Fe, Valencia, Spain; Aurelia Alexandru, MD, Institute of Oncology Prof Dr Alexandru Trestioreanu, Bucharest, Romania; Luis Paz-Ares, MD, Universidad Complutense de Madrid, Madrid, Spain; Shun Lu, MD, Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai, China; Martin Reck, MD, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany; Nan Hu, MS, Bristol Myers Squibb, Princeton, NJ; Xiaoqing Zhang, MD, PhD, Bristol Myers Squibb, Princeton, NJ; Diederik Johannes Grootendorst, PhD, Bristol Myers Squibb, Princeton, NJ; Laura Eccles, PhD, Bristol Myers Squibb, Princeton, NJ; Thomas John, MD, Austin Hospital, Heidelberg, Australia
BACKGROUND: First-line immunotherapy-based regimens have limited efficacy in patients with metastatic non–small-cell lung cancer (NSCLC) and tumor programmed death ligand 1 (PD-L1) <1%. A high unmet medical need remains in metastatic NSCLC, particularly in patients with squamous metastatic NSCLC or baseline brain metastasis. In CheckMate 9LA (NCT03215706), first-line nivolumab plus ipilimumab and 2 cycles of chemotherapy showed long-term, durable benefit versus chemotherapy in patients with metastatic NSCLC, regardless of tumor PD-L1 status.
OBJECTIVE: To report an exploratory analysis of efficacy and safety in patients with tumor PD-L1 of <1% by histology or the presence of brain metastasis.
METHOD: Adults with stage IV recurrent NSCLC, ECOG performance score of ≤1, and no sensitizing EGFR/ALK alterations were randomized 1:1 to first-line nivolumab (360 mg every 3 weeks) plus ipilimumab (1 mg/kg every 6 weeks) and chemotherapy (every 3 weeks for 2 cycles) or to chemotherapy alone (every 3 weeks for 4 cycles). Overall survival (OS), progression-free survival, objective response rate, duration of response, and safety were assessed in patients with tumor PD-L1 of <1% by histology (nonsquamous or squamous) or by the presence of baseline brain metastasis (by blinded independent central review).
RESULTS: Baseline characteristics of the patients with tumor PD-L1 of <1% were generally similar to the intention-to-treat population. With a minimum follow-up of 36.1 months (database lock, February 15, 2022), survival was improved with nivolumab plus ipilimumab and chemotherapy versus with chemotherapy alone in the subgroups of patients with tumor PD-L1 of <1% by histology or by the presence of brain metastasis. The median OS (nivolumab plus ipilimumab and chemotherapy vs chemotherapy) was 18.6 months vs 12.4 months in the nonsquamous disease subgroup (N = 99 vs N = 93, respectively; hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.54-1.02); 15.3 months vs 8.0 months in the squamous disease subgroup (N = 36 vs N = 36, respectively; HR, 0.50; 95% CI, 0.30-0.83); 20.6 months vs 6.9 months in the patients with brain metastasis (N = 17 vs N = 15, respectively; HR, 0.28; 95% CI, 0.13-0.61); and 16.4 months versus 11.2 months in the patients without brain metastasis (N = 118 vs N = 114, respectively; HR, 0.72; 95% CI, 0.54-0.96). A similar clinical benefit of nivolumab plus ipilimumab and chemotherapy in efficacy outcomes will be presented. No new safety signals were observed.
CONCLUSION: First-line nivolumab plus ipilimumab and chemotherapy showed long-term, durable clinical benefit in patients with metastatic NSCLC and tumor PD-L1 of <1%, regardless of histology or the presence of baseline brain metastasis. These exploratory results were consistent with previous reports from all randomized patients and further support the use of nivolumab plus ipilimumab and chemotherapy as a first-line treatment option for patients with metastatic NSCLC.
Supported by funding from Bristol Myers Squibb. Previously presented at the European Society for Medical Oncology (ESMO) 2022, Poster #1049P. Thomas John, et al.