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 ESMO Immuno-Oncology Congress 2019 in Geneva, Switzerland (11-14 December).
Prof. Fabrice Barlesi of the Multidisciplinary Oncology and Therapeutic Innovations, Aix-Marseille Université; CNRS, INSERM, CRCM, and Assistance Publique-Hôpitaux 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%. 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).
Prof. 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.
Treatment-related adverse events were similar between cohorts
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 817enrolled patients with previously untreated stage IV or recurrent NSCLC, and no known sensitising 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 one-year OS 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 (Figure below). In cohort A, the 18-month OS rate was 49% overall, 53% for patients with PD-L1 expression ≥1%, and 44% for those with PD-L1 expression <1%.
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.
This trial was sponsored by Bristol-Myers Squibb.
92O – Barlesi F, Audigier-Valette C, Felip E, et al. Nivolumab plus low-dose ipilimumab as first-line treatment of advanced NSCLC: overall survival analysis of CheckMate 817.