GENEVA, SWITZERLAND-First-line treatment with a combination of 240 mg Q2W flat-dose nivolumab and 1 mg/kg Q6W ipilimumab was safe and provided encouraging overall survival (OS) 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 ECOG performance status (PS). The findings were presented at the 2019 ESMO Immuno-Oncology Congress.
Fabrice Barlesi, MD, PhD, of the Multidisciplinary Oncology and Therapeutic Innovations, Aix-Marseille Universite; CNRS, INSERM, CRCM, and Assistance Publique-Hopitaux de Marseille in Marseille, France, introduced his presentation highlighting the Part 1 results of the CheckMate-227 trial, which met its primary endpoint of improving OS with first-line nivolumab plus ipilimumab versus standard chemotherapy in patients with advanced NSCLC and PD-L1 expression >=1 percent. In that trial, OS benefit was observed in patients across all programmed death ligand 1 (PD-L1) expression subgroups (>=1% and <1%), regardless of histology (non-squamous and squamous).
Barlesi and a team of investigators conducted the CheckMate-817 (NCT02869789) study to evaluate the combination of nivolumab/ipilimumab in first-line patients with advanced NSCLC and also in patients with specific comorbid conditions or poor PS.
CheckMate-817 is a multi-cohort, single arm, phase IIIb study evaluating the safety of flat-dose nivolumab plus a weight-based ipilimumab in patients with advanced NSCLC. Additional safety data and OS were reported at ESMO Immuno-Oncology Congress 2019 for cohorts A (ECOG PS 0-1) and A1 (co-morbidity or poor PS); preliminary safety and efficacy results have been reported previously.
The safety profile, which consisted of the type and rate of treatment-related adverse events (TRAEs), was consistent between the cohorts. The median time to onset of select TRAEs was 2 to 26 weeks in cohort A and 2 to 21 weeks in cohort A1. No new AEs were noted in the special populations (cohort A1). Select TRAEs generally resolved with guideline-based management. Nivolumab plus ipilimumab appeared generally well tolerated in cohort A1, despite co-morbidity or poor PS. Overall survival in cohort A was similar to CheckMate 227 Part 1; and cohort A1 had encouraging OS
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 PS 0-1, whereas cohort A1 comprised 198 patients considered as special populations, including ECOG PS 2, asymptomatic untreated brain metastases, hepatic or renal impairment, or HIV. Except for ECOG PS and co-morbidities, the baseline characteristics were similar between cohorts.
All of the patients were treated with nivolumab at 240 mg every 2 weeks plus ipilimumab at 1 mg/kg every 6 weeks for 2 years or until disease progression or unacceptable toxicity occurred. Safety in cohort A served as the primary endpoint and 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.
With a minimum follow-up of 21 months in cohort A and 14 months in cohort A1, the median OS was 17.0 months and 9.9 months, respectively. The 1-year OS rates were 60 percent for patients in cohort A (61% for those with PD-L1 expression >=1%; 58% for those with <1% expression), and 47 percent for patients in cohort A1. In cohort A, the 18-month OS rate was 49 percent overall, 53 percent for patients with PD-L1 expression >=1 percent, and 44 percent for those with PD-L1 expression <1 percent.
The authors noted that the select TRAE profile of nivolumab plus ipilimumab was similar between patients with advanced NSCLC in cohorts A and A1, wherein patients also had co-morbidity or poor PS.
First-line nivolumab and ipilimumab resulted in durable OS outcomes in cohort A patients with advanced NSCLC that were comparable to reported outcomes from CheckMate-227. Additionally, cohort A1 had promising OS outcomes, despite patients having poor performance status or co-morbidities.