Systemic and Intracranial Outcomes With First-Line Nivolumab Plus Ipilimumab in Patients With Metastatic NSCLC and Baseline Brain Metastases From CheckMate 227 Part 1.

In CheckMate 227 Part 1, nivolumab plus ipilimumab prolonged overall survival (OS) versus chemotherapy in patients with metastatic NSCLC, regardless of tumor programmed death-ligand 1 (PD-L1) expression. Here, we report post hoc exploratory systemic and intracranial efficacy outcomes and safety by baseline brain metastasis status at 5 years' minimum follow-up. Treatment-naive adults with stage IV or recurrent NSCLC without EGFR or ALK alterations, including asymptomatic patients with treated brain metastases, were enrolled. Patients with tumor PD-L1 greater than or equal to 1% were randomized to nivolumab plus ipilimumab, nivolumab, or chemotherapy; patients with tumor PD-L1 less than 1% were randomized to nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy groups. Assessments included OS, systemic and intracranial progression-free survival per blinded independent central review, new brain lesion development, and safety. Brain imaging was performed at baseline (all randomized patients) and approximately every 12 weeks thereafter (patients with baseline brain metastases only). Overall, 202 of 1739 randomized patients had baseline brain metastases (nivolumab plus ipilimumab: 68; chemotherapy: 66). At 61.3 months' minimum follow-up, nivolumab plus ipilimumab prolonged OS versus chemotherapy in patients with baseline brain metastases (hazard ratio = 0.63; 95% confidence interval: 0.43-0.92) and in those without (hazard ratio = 0.76; 95% confidence interval: 0.66-0.87). In patients with baseline brain metastases, 5-year systemic and intracranial progression-free survival rates were higher with nivolumab plus ipilimumab (12% and 16%, respectively) than chemotherapy (0% and 6%). Fewer patients with baseline brain metastases developed new brain lesions with nivolumab plus ipilimumab (4%) versus chemotherapy (20%). No new safety signals were observed. With all patients off immunotherapy for more than or equal to 3 years, nivolumab plus ipilimumab continued to provide a long-term, durable survival benefit in patients with or without brain metastases. Intracranial efficacy outcomes favored nivolumab plus ipilimumab versus chemotherapy. These results further support nivolumab plus ipilimumab as an efficacious first-line treatment for patients with metastatic NSCLC, regardless of baseline brain metastasis status

Safety of First-line Nivolumab Plus Ipilimumab in Patients With Metastatic Non-Small Cell Lung Cancer: A Pooled Analysis of CheckMate 227, CheckMate 568, and CheckMate 817.

We characterized first-line nivolumab plus ipilimumab (NIVO+IPI) safety in a large patient population with metastatic non-small cell lung cancer (NSCLC) and efficacy outcomes after NIVO+IPI discontinuation due to treatment-related adverse events (TRAEs). We pooled data from three first-line NIVO+IPI studies (NIVO, 3 mg/kg or 240 mg every 2 weeks; IPI, 1 mg/kg every 6 weeks) in metastatic NSCLC (CheckMate 227 Part 1, CheckMate 817 cohort A, CheckMate 568 Part 1). Safety endpoints included TRAEs and immune-mediated adverse events (IMAEs) in the pooled population and patients aged ≥75 years. In the pooled population (N=1255), any-grade TRAEs occurred in 78% of patients, grade 3/4 TRAEs in 34%, and discontinuations of any regimen component due to TRAEs in 21%. The most frequent TRAE and IMAE were diarrhea (20%; grade 3/4, 2%) and rash (17%; grade 3/4, 3%), respectively. The most common grade 3/4 IMAEs were hepatitis (5%) and diarrhea/colitis and pneumonitis (4% each). Pneumonitis was the most common cause of treatment-related death (5/16). Safety in patients aged ≥75 years (n=174) was generally similar to the overall population, but discontinuations of any regimen component due to TRAEs were more common (29%). In patients discontinuing NIVO+IPI due to TRAEs (n=225), 3-year overall survival was 50% (95% CI: 42.6-56.0), and 42% (31.2-52.4) of 130 responders remained in response 2 years after discontinuation. First-line NIVO+IPI was well tolerated in this large population with metastatic NSCLC and in patients aged ≥75 years. Discontinuations due to TRAEs did not reduce long-term survival