Nivolumab did not extend progression-free survival over chemotherapy in the first-line setting in patients with PD-L1–positive advanced non–small-cell lung cancer, according to results of an open-label phase III trial.
Nivolumab did not extend progression-free survival over chemotherapy in the first-line setting in patients with programmed cell death ligand 1 (PD-L1)-positive advanced non–small-cell lung cancer (NSCLC), according to results of an open-label phase III trial.
Previous studies have shown that nivolumab was better than chemotherapy in patients with metastatic NSCLC who had progressed during or after platinum-based chemotherapy. “Benefit was seen regardless of the PD-L1 expression level but was enhanced in patients with nonsquamous NSCLC with increasing PD-L1 expression,” wrote study authors led by David P. Carbone, MD, PhD, of the Ohio State University Comprehensive Cancer Center in Columbus.
The new study compared nivolumab as first-line therapy in patients with PD-L1 expression levels of 5% or more. Investigators randomized 541 patients with expression levels of 1% or more to receive either nivolumab (271 patients) or platinum-based chemotherapy (270 patients), and the primary efficacy analysis included the 423 patients who met the 5% expression cut-off. Results of the study were published online ahead of print in the New England Journal of Medicine.
There were two notable differences with regard to the treatment characteristics of the two groups of patients: there were more women in the chemotherapy group (45% vs 32%), and there were more patients with PD-L1 expression level of 50% or more (47% vs 32%) in the chemotherapy group.
After a median follow-up of 13.5 months, the median progression-free survival was 4.2 months with nivolumab, and 5.9 months with chemotherapy, for a hazard ratio (HR) of 1.15 (95% CI, 0.91–1.45; P = .25). Median overall survival was 14.4 months with nivolumab, compared to 13.2 months with chemotherapy, for an HR of 1.02 (95% CI, 0.80–1.30); 60% of chemotherapy patients subsequently received nivolumab, which authors wrote could have contributed to the relatively long overall survival in these patients. There were numerically more responses to therapy with chemotherapy, at 33% compared with 26% with nivolumab.
A subgroup analysis of those with PD-L1 expression of 50% or more again showed no significant difference between the therapies. However, the imbalance in gender was even more pronounced, at 44% in the chemotherapy group and 25% in the nivolumab group.
Treatment-related adverse events (AEs) occurred in 71% of nivolumab patients and in 92% of chemotherapy patients, and grade 3/4 AEs were also less common with nivolumab (18% vs 51%). Treatment-related serious AEs occurred at similar rates, and treatment-related AEs that led to drug discontinuation occurred in 10% of nivolumab patients and in 13% of chemotherapy patients. Two nivolumab and three chemotherapy patients died in events attributed to treatment.
“The correlation between tumor PD-L1 expression and efficacy of this drug class is imperfect and differs according to tumor type and according to trial,” wrote Edward B. Garon, MD, of the University of California, Los Angeles, in an accompanying editorial. Better biomarker-based selection of patients is still needed. “If the strategies for the selection of patients in clinical practice differ significantly from proven approaches, the data suggest that our patients may not derive the same benefits as have been seen in clinical trials.”