First-line treatment with the combination of nivolumab and ipilimumab was safe and provided encouraging overall survival results in patients with advanced non–small cell lung cancer (NSCLC), as well as in patients with NSCLC traditionally not eligible for clinical trials—such as those who had either a comorbid condition or poor Eastern Cooperative Oncology Group (ECOG) performance status. The findings were presented by Barlesi et al at the European Society for Medical Oncology (ESMO) Immuno-Oncology Congress 2019 (Abstract 92O).

Fabrice Barlesi, MD, PhD

Fabrice Barlesi, MD, PhD, of Aix-Marseille Université and Assistance Publique-Hôpitaux de Marseille, first highlighted results from the CheckMate 227 trial, which met its primary endpoint of improving overall survival with first-line nivolumab/ipilimumab vs standard chemotherapy in patients with advanced NSCLC and programmed cell death ligand 1 (PD-L1) expression ≥ 1%. In that trial, overall survival benefit was observed in patients across all PD-L1 expression subgroups (≥ 1% and < 1%), regardless of histology (nonsquamous or squamous).

CheckMate 817

Dr. Barlesi and a team of investigators conducted the CheckMate 817 study to evaluate the combination of nivolumab/ipilimumab in first-line patients with advanced NSCLC, as well as in patients with specific comorbid conditions or poor performance statu. CheckMate 817 is a multicohort, single-arm, phase IIIb study evaluating the safety of flat-dose nivolumab plus a weight-based dose of ipilimumab in patients with advanced NSCLC.

CheckMate 817 enrolled patients with previously untreated stage IV or recurrent NSCLC and no known sensitizing EGFR or ALK alterations. The patients were unselected for PD-L1 expression status. The 391 patients in cohort A had ECOG performance status 0–1, whereas cohort A1 comprised 198 patients considered as special populations, including those with ECOG performance status 2, asymptomatic untreated brain metastases, hepatic or renal impairment, or human immunodeficiency virus. Except for ECOG performance status and comorbidities, the baseline characteristics were similar between cohorts.

All of the patients were treated with 240 mg of nivolumab every 2 weeks plus 1 mg/kg of ipilimumab every 6 weeks for 2 years, or until disease progression or unacceptable toxicity occurred. Safety in cohort A served as the primary endpoint; the secondary endpoint was efficacy; exploratory endpoints included safety and efficacy in cohort A1 along with biomarker analyses, inclusive of PD-L1 expression for both cohorts.

Additional safety and overall survival data were reported at the ESMO Immuno-Oncology Congress 2019 for cohorts A and A1; preliminary safety and efficacy results have been reported previously.

Safety

The safety profile—which consisted of the type and rate of treatment-related adverse events—was consistent between the cohorts. The median time to onset of select treatment-related adverse events was 2 to 26 weeks in cohort A, and 2 to 21 weeks in cohort A1. No new adverse events were noted in any special populations. Select treatment-related adverse events generally resolved with guideline-based management. Nivolumab/ipilimumab appeared generally well tolerated in cohort A1, despite comorbidity or poor performance status.

Survival

With a minimum follow-up of 21 months in cohort A and 14 months in cohort A1, the median overall survival was 17.0 months and 9.9 months, respectively. The 1-year overall survival rates were 60% for patients in cohort A (61% for those with PD-L1 expression ≥ 1%; 58% for those with < 1% expression), and 47% for patients in cohort A1. In cohort A, the 18-month overall survival rate was 49% overall, 53% for patients with PD-L1 expression ≥ 1%, and 44% for those with PD-L1 expression < 1%.

The authors concluded that the select treatment-related adverse event profile of nivolumab/ipilimumab was similar between patients with advanced NSCLC in cohorts A and A1. They also noted first-line nivolumab/ipilimumab resulted in durable overall survival outcomes in cohort A that were comparable to reported outcomes from CheckMate 227. Additionally, cohort A1 had promising overall survival outcomes, despite patients having poor performance status or comorbidities.

Disclosure: The trial was sponsored by Bristol-Myers Squibb. For full disclosures of the study authors, visit oncologypro.esmo.org.