The CheckMate 9LA trial demonstrated that treatment of patients with metastatic non–small-cell lung cancer (NSCLC) with nivolumab plus ipilimumab combined with 2 cycles of chemotherapy improved survival benefits compared with treatment of 4 cycles of chemotherapy alone.1 In a late-breaking presentation at the 2022 American Society of Clinical Oncology Annual Meeting, Paz Ares and colleagues reported updated 3-year efficacy and safety data, and the results of exploratory biomarker analyses.2
CheckMate 9LA enrolled patients with stage IV or recurrent NSCLC with no known sensitizing EGFR/ALK alterations and an Eastern Cooperative Oncology Group performance status of 0 or 1.2 The patients were randomized 1:1 to nivolumab 360 mg every 3 weeks plus ipilimumab 1 mg/kg every 6 weeks plus 2 cycles of chemotherapy (n = 361) or 4 cycles of platinum-based chemotherapy alone (n = 358).2
Patients were stratified by tumor PD-L1 expression level, sex, and histology. Patients with nonsquamous NSCLC in the chemotherapy-alone arm could receive pemetrexed maintenance. The study assessed overall survival (OS), progression-free survival (PFS), and objective response rate.2 For all patients with nonsquamous NSCLC and with tissue evaluable for mutational analysis (n = 313), the FoundationOne CDx™ assay was used to identify mutant (mut) or wild-type (wt) KRAS and STK11 genes. Exploratory assessments included evaluation of OS and PFS with nivolumab plus ipilimumab in combination with chemotherapy versus chemotherapy by mutation status and safety.2
At a minimum follow-up of 36.1 months, patients continued to derive long-term, durable OS benefits with nivolumab plus ipilimumab combined with 2 cycles of chemotherapy versus chemotherapy alone (hazard ratio, 0.74; 95% confidence interval, 0.62-0.87); 3-year OS rates were 27% versus 19%, respectively. The clinical benefit of nivolumab plus ipilimumab combined with 2 cycles of chemotherapy versus chemotherapy alone was observed in all randomized patients and across most subgroups, including by PD-L1 expression level or histology.2 The 3-year OS rates for the nivolumab/ipilimumab/limited chemotherapy regimen versus chemotherapy alone among patients with PD-L1 <1%, PD-L1 ≥1%, PD-L1 1%-49%, and PD-L1 ≥50% were 25% versus 15%, 28% versus 19%, 26% versus 15%, and 33% versus 24%, respectively.
In an exploratory analysis based on KRAS and STK11 mutation status, nivolumab plus ipilimumab combined with 2 cycles of chemotherapy improved OS versus chemotherapy alone (median OS, 16.3 vs 13.1 months). Similar trends of prolonged OS were also observed in patients with or without KRAS mutation (median OS, mut, 19.2 vs 13.5 months; wt, 15.6 vs 12.7 months) or STK11 mutation (mut, 13.8 vs 10.7 months; wt, 17.8 vs 13.9 months), respectively. No new safety signals were observed.2
In conclusion, the 3-year follow-up of CheckMate 9LA demonstrated that first-line nivolumab plus ipilimumab combined with 2 cycles of chemotherapy provided long-term, durable OS benefit versus chemotherapy alone in patients with metastatic NSCLC.2 Survival benefit of the combination regimen was observed regardless of PD-L1 level and was effective even in PD-L1–negative patients.
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