Nivolumab + ipilimumab safe first-line treatment for NSCLC patients with comorbidities

Data from the CHECKMATE-817 trial demonstrated that the combination of nivolumab and ipilimumab is a safe first-line treatment option for patients with advanced non-small-cell lung cancer (NSCLC) who also harbour comorbidities or a poor Eastern Cooperative Oncology Group (ECOG) performance status. The combination was shown to have a consistent safety profile in these special populations.

Until recently, data on immunotherapy in patients with advanced NSCLC and poor performance status or other comorbidities were limited. CheckMate 817 –a multi-cohort, open-label phase 3b/4 study– investigated safety and efficacy of flat-dose nivolumab + weight-based low-dose ipilimumab in patients with advanced NSCLC. Dr Fabrice Barlesi (Hôpitaux de Marseille, France) evaluated this regimen as first-line treatment in a reference population (cohort A, n=391, ECOG performance status 0-1) and a special population (cohort A1, n=198) consisting of patients with ECOG performance status 2 (n=139) or ECOG performance status 0-1 and one of the following comorbidities (n=59): asymptomatic untreated brain metastases, hepatic or renal impairment, or human immunodeficiency virus (HIV). Baseline characteristics were generally balanced between cohorts. Treatment consisted of nivolumab 240 mg Q2W + ipilimumab 1 mg/kg Q6W for two years or until disease progression or unacceptable toxicity [1].

Although grade 3-4 treatment-related adverse events (AEs) were similar between cohorts, they were higher within cohort A1 for patients with comorbidities compared with those with ECOG performance status 2 (34% vs 24%). However, treatment-related AEs leading to discontinuation were similar across populations (12% for patients treated in cohort A1 with ECOG PS 2 and 12% for all other special populations, and 13% for all patients in cohort A). With regard to efficacy, objective response rate was 25% in cohort A1 (20% for patients with ECOG PS 2 and 37% for all other special populations) and 35% in cohort A. Progression-free survival was numerically shorter in cohort A1 than cohort A; high tumour mutation burden (TMB) (≥10 mut/Mb) and higher programmed death-ligand 1 (PD-L1) expression (≥1% or ≥50%) were associated with numerically longer progression-free survival in both cohorts. Dr Barlesi concluded that first-line flat-dose nivolumab + weight-based ipilimumab showed a consistent safety profile in special populations with advanced NSCLC, including those with ECOG performance status 2.

1. Barlesi F, et al. OA04.02. WCLC 2019.

Posted on 8 November 20195 March 2021