First-line nivolumab plus ipilimumab with two cycles of chemotherapy versus chemotherapy alone (four cycles) in advanced non-small-cell lung cancer: CheckMate 9LA 2-year update

M. Reck (1) , T.-E. Ciuleanu (2) , M. Cobo (3) , M. Schenker (4) , B. Zurawski (5) , J. Menezes (6) , E. Richardet (7) , J. Bennouna (8) , E. Felip (9) , O. Juan-Vidal (10) , A. Alexandru (11) , H. Sakai (12) , A. Lingua (13) , F. Reyes (14) , P.-J. Souquet (15) , P. de Marchi (16) , C. Martin (17) , M. Pérol (18) , A. Scherpereel (19) , S. Lu (20) , L. Paz-Ares (21) , D.P. Carbone (22) , A. Memaj (23) , S. Marimuthu (23) , X. Zhang (23) , P. Tran (23) , T. John (24)

1 German Center for Lung Research
2 Institutul oncologic Prof Dr Ion Chiricuta [Cluj-Napoca, Romania]
3 IBIMA Plataforma BIONAND - Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina = Biomedical Research Institute of Málaga and Nanomedicine Platform
4 SF Nectarie Oncology Center [Craiova, Romania]
5 AC - Ambulatorium Chemioterapii [Bydgoszcz, Poland]
6 HNSDC - Hospital Nossa Senhora Da Conceição [Porto Alegre, Brazil]
7 IODC - Instituto Oncológico De Córdoba [Córdoba, Argentina]
8 CRCINA-ÉQUIPE 4 - Immunogenic Cell Death and Mesothelioma Therapy
9 Vall d'Hebron University Hospital [Barcelona]
10 Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe
11 OIB - Oncology Institute of Bucharest Professor Doctor Alexandru Trestioreanu [Bucharest, Romania]
12 S2C - Saitama Cancer Center [Saitama, Japan]
13 IMRC - Instituto Medico Rio Cuarto SA [Córdoba, Argentina]
14 FALP - Fundacion Arturo Lopez Perez [Santiago, Metropolitana, Chile]
15 CHLS - Centre Hospitalier Lyon Sud [CHU - HCL]
16 BCH - Barretos Cancer Hospital [São Paulo, Brazil]
17 IAF - Instituto Alexander Fleming [Buenos Aires, Argentina]
18 Centre Léon Bérard [Lyon]
19 ONCO-THAI - Thérapies Laser Assistées par l'Image pour l'Oncologie - U 1189
20 Shangaï Jiao Tong University [Shangaï]
21 Hospital Universitario 12 de Octubre [Madrid]
22 OSU - Ohio State University [Columbus]
23 Bristol-Myers Squibb [Princeton]
24 Austin Hospital [Melbourne]

Background: To further characterize survival benefit with first-line nivolumab plus ipilimumab with two cycles of chemotherapy versus chemotherapy alone, we report updated data from the phase III CheckMate 9LA trial with a 2-year minimum follow-up. Patients and methods: Adult patients were treatment naïve, with stage IV/recurrent non-small-cell lung cancer, no known sensitizing EGFR/ALK alterations, and an Eastern Cooperative Oncology Group performance status ≤1. Patients were randomized 1 : 1 to nivolumab 360 mg every 3 weeks plus ipilimumab 1 mg/kg every 6 weeks with two cycles of chemotherapy, or four cycles of chemotherapy. Updated efficacy and safety outcomes are reported, along with progression-free survival (PFS) after next line of treatment (PFS2), treatment-related adverse events (TRAEs) by treatment cycle, and efficacy outcomes in patients who discontinued all treatment components in the experimental arm due to TRAEs. Results: With a median follow-up of 30.7 months, nivolumab plus ipilimumab with chemotherapy continued to prolong overall survival (OS) versus chemotherapy. Median OS was 15.8 versus 11.0 months [hazard ratio 0.72 (95% confidence interval 0.61-0.86)]; 2-year OS rate was 38% versus 26%. Two-year PFS rate was 20% versus 8%. ORR was 38% versus 25%, respectively; 34% versus 12% of all responses were ongoing at 2 years. Median PFS2 was 13.9 versus 8.7 months. Improved efficacy outcomes in the experimental versus control arm were observed across most subgroups, including by programmed death-ligand 1 and histology. No new safety signals were observed; onset of grade 3/4 TRAEs was mostly observed during the first two treatment cycles in the experimental arm. In patients who discontinued all components of nivolumab plus ipilimumab with chemotherapy treatment due to TRAEs (n = 61) median OS was 27.5 months; 56% of responders had an ongoing response ≥1 year after discontinuation. Conclusions: With a 2-year minimum follow-up, nivolumab plus ipilimumab with two cycles of chemotherapy provided durable efficacy benefits over chemotherapy with a manageable safety profile and remains an efficacious first-line treatment of advanced non-small-cell lung cancer.

Mots clés: NSCLC; dual immunotherapy; first-line; ipilimumab; nivolumab.

Domaines: Cancer

M. Reck, T.-E. Ciuleanu, M. Cobo, M. Schenker, B. Zurawski, et al.. First-line nivolumab plus ipilimumab with two cycles of chemotherapy versus chemotherapy alone (four cycles) in advanced non-small-cell lung cancer: CheckMate 9LA 2-year update. ESMO Open, 2021, 6 (5), pp.100273. ⟨10.1016/j.esmoop.2021.100273⟩. ⟨inserm-03540859⟩