Hellmann MD, et al. - Authors evaluated the progression-free survival with nivolumab plus ipilimumab compared to chemotherapy among non–small-cell lung cancer (NSCLC) patients with a high tumour mutational burden (≥10 mutations per megabase). Among patients with NSCLC and a high tumour mutational burden, irrespective of programmed death ligand 1 (PD-L1) expression level, significantly longer progression-free survival was seen with first-line nivolumab plus ipilimumab vs with chemotherapy. The benefit of nivolumab plus ipilimumab in NSCLC and the role of a tumour mutational burden as a biomarker for patient selection were validated in the findings.

Methods

• Researchers enrolled patients with stage IV or recurrent NSCLC that was not previously treated with chemotherapy.
• They randomly assigned those with a level of tumor programmed death ligand 1 (PD-L1) expression of at least 1%, in a 1:1:1 ratio, to receive nivolumab plus ipilimumab, nivolumab monotherapy, or chemotherapy.
• Experts randomly assigned those with a tumor PD-L1 expression level of less than 1%, in a 1:1:1 ratio, to receive nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy.
• The FoundationOne CDx assay determined the tumor mutational burden.

Results

• As per the findings, among patients with a high tumor mutational burden, progression-free survival was significantly longer with nivolumab plus ipilimumab than with chemotherapy.
• Findings suggested that the 1-year progression-free survival rate was 42.6% with nivolumab plus ipilimumab vs 13.2% with chemotherapy, and the median progression-free survival was 7.2 months (95% confidence interval [CI], 5.5 to 13.2) vs 5.5 months (95% CI, 4.4 to 5.8) (hazard ratio for disease progression or death, 0.58; 97.5% CI, 0.41 to 0.81; P < 0.001).
• Authors noted the objective response rate to be 45.3% with nivolumab plus ipilimumab and 26.9% with chemotherapy.
• Broadly consistent benefit of nivolumab plus ipilimumab was seen within subgroups, including patients with a PD-L1 expression level of at least 1% and those with a level of less than 1% compared to chemotherapy.
• With nivolumab plus ipilimumab, the rate of grade 3 or 4 treatment-related adverse events was 31.2% and 36.1% with chemotherapy.