Nivolumab failed to provide an additional survival benefit compared with chemotherapy among patients with previously untreated or recurrent stage IV non–small cell lung cancer (NSCLC), according to results from the CheckMate 026 trial published in the New England Journal of Medicine.1
Nivolumab is already approved for the second-line treatment of metastatic NSCLC and is associated with prolonged overall survival (OS) among this population. The CheckMate 026 trial (ClinicalTrials.gov Identifier: NCT02041533) evaluated nivolumab in the first-line setting.
The open-label, phase 3 trial randomly assigned 530 patients with previously untreated or recurrent stage IV NSCLC with at least 1% PD-L1 tumor expression to receive nivolumab or platinum-based chemotherapy. Crossover to the nivolumab arm was allowed for patients who progressed during chemotherapy.
The median age at baseline was 64 and 11% of patients were age 75 or older. The disease stage was IV among 92% of patients and recurrent among 8%, and 24% and 76% of patients had squamous or nonsquamous cell histology, respectively.
The majority of patients were former smokers (68%), followed by current smokers (20%), and never smokers (11%). PD-L1 tumor expression was at least 5% among 77% and 50% or higher among 40% of patients.
The response rate was 26% with nivolumab and 33% with chemotherapy among patients with at least 5% PD-L1 tumor expression.
There was no significant difference in progression-free survival (PFS) between arms among patients with at least 5% PD-L1 tumor expression, which was the primary endpoint (hazard ratio [HR], 1.15; 95% CI, 0.91-1.45; P = .25).
The median PFS was 4.2 months (95% CI, 3.0-5.6 months) with nivolumab compared with 5.9 months (95% CI, 5.4-6.9 months) with chemotherapy.
The median OS was also similar between groups, at 14.4 months (95% CI, 11.7-17.4 months) with nivolumab compared with 13.2 months (95% CI, 10.7-17.1) with chemotherapy (HR for death, 1.02; 95% CI, 0.80-1.30).
These data were similar among all patients who were randomly assigned, which included those with PD-L1 tumor expression of at least 1%.
Adverse events (AEs) occurred more frequently with chemotherapy, with 92% and 51% of patients experiencing AEs of any grade or grade 3-4, respectively, with chemotherapy compared with 71% and 18% with nivolumab.
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Discontinuation of therapy due to AEs occurred among 10% of patients in the nivolumab arm compared with 13% in the chemotherapy arm.
These results suggest that first-line treatment of advanced NSCLC with nivolumab does not prolong PFS or OS compared with chemotherapy, though nivolumab had a better safety profile.
- Carbone DP, Reck M, Paz-Ares L, et al. First-line nivolumab in stage IV or recurrent non-small-cell lung cancer. N Engl J Med. 2017;376:2415-26. doi: 10.1056/NEJMoa1613493