Two-Year Update from CheckMate-9LA Study of Nivolumab plus Ipilimumab in Advanced NSCLC

With 2 years’ minimum follow-up, first-line use of nivolumab, ipilimumab, and chemotherapy offers durable survival relative to chemotherapy alone in patients with advanced non–small-cell lung cancer.

In the randomized phase 3 CheckMate-9LA trial, combination use of nivolumab (NIVO) and ipilimumab (IPI) plus 2 cycles of chemotherapy significantly improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) compared with chemotherapy alone (4 cycles) as first-line therapy for patients with advanced non–small-cell lung cancer (NSCLC). Clinical benefit was observed regardless of PD-L1 expression level and histology. At the American Society of Clinical Oncology 2021 annual meeting, researchers reported efficacy data with at least 2 years’ follow-up from the CheckMate-9LA study.1

Adult patients with stage IV recurrent NSCLC, Eastern Cooperative Oncology Group performance status of 0 or 1, and no known sensitizing EGFR or ALK alterations were stratified by PD-L1 score (<1% vs ≥1%), sex, and histology (squamous vs nonsquamous). They were randomized 1:1 to NIVO 360 mg every 3 weeks plus IPI 1 mg/kg every 6 weeks plus chemotherapy (2 cycles; n = 361) or chemotherapy alone (4 cycles; n = 358). Patients with nonsquamous NSCLC in the chemotherapy-alone arm could receive pemetrexed maintenance. The primary end point was OS. Secondary end points included PFS and ORR by blinded independent central review, and efficacy by different PD-L1 levels. Safety was exploratory.1

After minimum follow-up of 24.4 months for OS (database lock, February 18, 2021), patients treated with NIVO + IPI + chemotherapy continued to derive OS benefit compared with chemotherapy.1 The median OS for each arm was 15.8 months versus 11.0 months, respectively (hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.61-0.86).1 Two-year OS rates were 38% versus 26%, respectively.1

Median PFS with NIVO + IPI + chemotherapy versus chemotherapy was 6.7 months compared with 5.3 months for chemotherapy alone (HR, 0.67; 95% CI, 0.56-0.79); 8% and 37% of patients who had disease progression received subsequent immunotherapy, respectively.1 ORR was 38% with NIVO + IPI + chemotherapy compared with 25% with chemotherapy.1 Similar clinical benefit with NIVO + IPI + chemotherapy versus chemotherapy was observed in all randomized patients and across the majority of subgroups, including by PD-L1 expression level and histology.1

Any grade and grade 3/4 treatment-related adverse events were reported in 92% and 48% of patients in the NIVO + IPI + chemotherapy arm, respectively, compared with 88% and 38% in the chemotherapy arm.1

Researchers concluded that after 2 years’ minimum follow-up, first-line NIVO + IPI + chemotherapy demonstrated durable survival and other efficacy benefits relative to chemotherapy alone in patients with advanced NSCLC. No new safety signals were identified.1


1. Reck M, Ciuleanu T-E, Cobo M, et al. First-line nivolumab (NIVO) plus ipilimumab (IPI) plus two cycles of chemotherapy (chemo) versus chemo alone (4 cycles) in patients with advanced non-small cell lung cancer (NSCLC): two-year update from CheckMate 9LA. Presented at: 2021 American Society of Clinical Oncology (ASCO) Annual Meeting; June 4-8, 2021. Abstract 9000.