Five-year Outcomes with First-Line Nivolumab Plus Ipilimumab with 2 Cycles of Chemotherapy Versus 4 Cycles of Chemotherapy Alone in Patients with Metastatic Non-Small Cell Lung Cancer in the Randomized CheckMate 9LA Trial

Background: We report 5-year efficacy and safety outcomes from CheckMate 9LA in patients with metastatic non- small cell lung cancer (mNSCLC) and exploratory analyses in key patient subgroups. Methods: Adults with stage IV/recurrent NSCLC and no sensitizing EGFR/ALK alterations were randomized to receive nivolumab plus ipilimumab with chemotherapy (n n = 361) or chemotherapy (n n = 358). Outcomes were assessed in all randomized patients and subgroups. Results: With 57.3 months' minimum follow-up, patients continued to derive overall survival (OS) benefit with nivolumab plus ipilimumab with chemotherapy over chemotherapy (HR, 0.73; 95% CI, 0.62-0.85; 5-year OS rates, 18% vs. 11%), regardless of tumor programmed death ligand 1 (PD-L1) expression (PD-L1 < 1%, 22% vs. 8%; PD-L1 >= 1%, 18% vs. 11%), histology (squamous, 18% vs. 7%; non-squamous, 19% vs. 12%), or presence of baseline brain metastases (20% vs. 6%). Five-year duration of response (DOR) rates were 19% versus 8% with nivolumab plus ipilimumab with chemotherapy versus chemotherapy, with consistent benefit across subgroups. Patients who discontinued nivolumab plus ipilimumab with chemotherapy due to treatment-related adverse events had a 5-year OS rate of 37%. Five-year progression-free survival and DOR rates in 5-year survivors were 55% versus 38% and 59% versus 46%, respectively. No new safety signals were observed in 5-year survivors, regardless of the number of ipilimumab doses received. Conclusion: This 5-year update supports the long-term, durable OS benefit and improved 5-year survivorship with nivolumab plus ipilimumab with chemotherapy over chemotherapy in patients with mNSCLC, regardless of tumor PD-L1 expression or histology. ClinicalTrials.gov registration: NCT03215706