Inhibition of programmed death 1 (PD-1) with pembrolizumab was well tolerated and showed promising survival results in a large phase I trial of patients with advanced non–small-cell lung cancer (NSCLC). The study found a cutoff for a biomarker that could be predictive of better results with the drug.
“One hallmark of cancer is immune evasion, in which the immune system does not mount an effective antitumor response,” wrote study authors led by Edward B. Garon, MD, of the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles. Inhibiting PD-1 can disrupt tumors’ ability to escape T-cell–induced antitumor activity; previous studies, however, have not formally validated PD ligand 1 (PD-L1) as a potential biomarker for success of this therapeutic target.
In the new study, 495 patients received the PD-1 inhibitor pembrolizumab and were assigned to either a training group (182 patients) or a validation group (313 patients); the median duration of follow-up was 10.9 months, and 115 patients continued on the therapy at the time of data cutoff. The results were published online ahead of print in the New England Journal of Medicine.
The overall response rate in the full cohort was 19.4%; it was higher in those who had not received any previous treatment (24.8% of 101 patients) than in previously treated patients (18.0% of 394 patients). The median duration of response was 12.5 months in the full cohort, and 23.3 months and 10.4 months in previously untreated and treated patients, respectively. The median overall survival was 12.0 months.
Based on results from the training cohort, a PD-L1 expression level of 50% of tumor cells was set. A total of 73 evaluable patients in the validation cohort met that cutoff—the response rate in those patients was 45.2%, exceeding response rates for patients with PD-L1 levels below that cutoff.
Most treated patients (70.9%) experienced some treatment-related adverse events; the most common were fatigue, pruritus, and decreased appetite. Only 9.5% experienced an adverse event of grade 3 or higher. Grade 3 or higher pneumonitis occurred in 9 patients (1.8%), including one who died. The authors said that overall the drug showed “modest toxicity.”
The study initially screened 1,143 patients, and 824 of those had samples that could be evaluated to determine how many patients might meet the PD-L1 expression cutoff: a total of 23.2% had a proportion score of at least 50%.
“This finding suggests that a proportion score of at least 50% may represent a new biomarker for the treatment of non–small-cell lung cancer,” the authors wrote. “Prospective testing of PD-L1 expression is feasible and retrospectively identified patients with an enhanced likelihood of having a clinical benefit from treatment with pembrolizumab.”