A programmed death 1 (PD-1) inhibitor is associated with similar efficacy to chemotherapy in patients with non-small cell lung cancer (NSCLC), but improves response rates and survival times in subgroups of patients, according to research published in New England Journal of Medicine (published online June 22, 2017; doi:10.1056/NEJMoa1613493).
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Nivolumab—a PD-1 immune checkpoint inhibitor antibody—has previously been linked to longer overall survival (OS) than chemotherapy among patients with previously-treated NSCLC. Clinical benefits of nivolumab may be increased for patients with at least 5% higher levels of programmed death ligand-1 (PD-L1) expression.
David P Carbone, MD, PhD, Ohio State University Comprehensive Cancer Center, and colleagues evaluated 423 patients with untreated stage IV or recurrent NSCLC and a PD-L1 expression level of at least 5%. Patients were randomized to receive either nivolumab intravenously at a dose of 3 mg per kilogram of body weight once every 2 weeks, or platinum-based chemotherapy once every 3 weeks for up to 6 cycles.
The researchers indicated the primary end point as progression-free survival (PFS) among patients with a PD-L1 expression level of 5% or more.
In the primary efficacy analysis, median PFS was 4.2 months with nivolumab compared with 5.9 months with chemotherapy, and the median OS was 14.4 months with nivolumab compared with 13.2 months with chemotherapy.
Among patients with a PD-L1 expression level of 5% or more, patients receiving nivolumab demonstrated lower response rates, but a higher percentage achieved a better response of progressive disease compared with those receiving chemotherapy. Patients in the nivolumab group had a median response duration of 12.1 months, whereas those in the chemotherapy group had a median response duration of 5.7 months.
Approximately 75% of patients with both a high tumor-mutation burden and a PD-L1 expression level of at least 50% responded to nivolumab therapy, compared with 32% among patients exhibiting high mutation burden, 34% with only high PD-L1 levels, and 16% with neither factor. Researchers acknowledged that immunotherapy may be more efficacious for patients with high tumor-mutation burden, but further investigation is needed.
“This study is an important step toward understanding the impact of tumor mutation burden and PDL-1 in immunotherapy response,” said Dr Carbone in the press statement (June 22, 2017). “This data shows we should evaluate these two factors independently to most accurately define who will benefit from immunotherapy.”—Christina Vogt
