First-line immunotherapy demonstrated significant benefit in patients with non-small cell lung cancer (NSCLC) who had both high tumor mutation burden and high programmed death ligand 1 (PD-L1)-positive status.
In an open-label phase 3 trial, investigators compared first-line nivolumab (Opdivo) with standard of care with chemotherapy in patients with PD-L1-positive NSCLC.
The study, published in the New England Journal of Medicine, included patients with untreated stage IV or recurrent NSCLC and a PD-L1 tumor expression level of 1% of more randomized to receive either nivolumab intravenously––at a dose of 4 mg per kilogram of body weight––once every 2 weeks, or platinum-based chemotherapy administered once every 3 weeks for up to 6 cycles.
Patients in the chemotherapy arm were permitted to cross over to receive nivolumab at the time of disease progression.
The primary endpoint was progression-free survival (PFS) among patients with PD-L1 expression level of 5% or more, as assessed by a blinded independent central review.
Among 423 patients with a PD-L1 level of 5% or more, the results of the study showed that the median PFS was 4.2 months in the nivolumab arm compared with 5.8 months in the chemotherapy arm. The median overall survival was 14.4 months in the nivolumab arm versus 13.3 months in the chemotherapy arm.
Overall, 60% of patients in the chemotherapy arm received nivolumab as subsequent therapy.
Patients with both high tumor mutation burden and high PD-L1-positive status had a 75% response rate compared with a 16% response rate among patients with low mutation burden and low PD-L1.
Treatment-related adverse events (AEs) of any grade were reported in 71% of patients who received nivolumab and in 92% who received chemotherapy. Treatment-related AEs of grade 3 or 4 occurred in 18% of patients in the nivolumab arm and 51% in the chemotherapy arm.
“Nivolumab was not associated with significantly longer progression-free survival than chemotherapy among patients with previously untreated stage IV or recurrent NSCLC with a PD-L1 expression level of 5% or more,” the authors wrote. “Overall survival was similar between groups. Nivolumab had a favorable safety profile, as compared with chemotherapy, with no new or unexpected safety signals.”
The authors noted that using genomic testing to better understand a patient’s overall tumor burden, could help identify which patients would most likely benefit from immunotherapy prior to the start of treatment.
“This study is an important step toward understanding the impact of tumor mutation burden and PD-L1 in immunotherapy response,” said lead investigator David Carbon, MD, PhD. “This data shows we should evaluate these 2 factors independently to most accurately define who will benefit from immunotherapy.”