PHILADELPHIA — The immunotherapy pembrolizumab was found to be safe and yielded durable responses in patients with advanced, non-small cell lung cancer (NSCLC), and those with high levels of the protein PD-L1 in their tumors had better clinical outcomes, according to phase I KEYNOTE-001 clinical trial data presented here at the AACR Annual Meeting 2015, April 18-22.
This study is being simultaneously published in the New England Journal of Medicine.
“Results from the training cohort of KEYNOTE-001 [reported last year at the AACR Annual Meeting 2014] to assess PD-L1 expression in tumor cells as a biomarker showed that NSCLC patients whose tumors expressed PD-L1 by immunohistochemistry in at least half of the cancer cells had the most favorable outcomes with pembrolizumab treatment,” said Edward B. Garon, MD, associate professor of medicine at the David Geffen School of Medicine at the University of California, Los Angeles. “We are now reporting data on all 495 patients in the trial, which includes 182 patients from the training cohort and 313 patients from the validation cohort.
“The overall response rate [ORR] for the entire 495 patients was 19 percent,” Garon noted. “The median duration of response exceeded a year among responders regardless of the degree of PD-L1 expression, which is one of the exciting outcomes with this class of drug.”
Approximately a quarter of screened patients had PD-L1 expression in at least half of their tumor cells. Among these patients in the validation cohort, the ORR was nearly 50 percent, Garon added. “In addition to being the largest data set of lung cancer patients treated with a checkpoint inhibitor, this is the first confirmation in an independent validation cohort that PD-L1 expression is clearly a marker of response,” he said.
For patients with 1 percent to 49 percent and less than 1 percent tumor PD-L1 expression, the ORRs were 16.5 percent and 10.7 percent, respectively.
After a median of 10.9 months of follow-up, among patients with PD-L1 expression in at least half of their cancer cells, the median overall survival has not been reached in those who were treatment-naïve or those who had been previously treated.
In general, the side effect profile was favorable, with less than 10 percent of patients experiencing grade 3 or greater drug-related adverse events, Garon noted. There was one drug-related death, resulting from pneumonitis, which was seen in 3.6 percent of patients, being grade 1 or 2 in half of the cases. Other immune-related adverse events occurring in at least 2 percent of the patients were infusion reactions and hypothyroidism.
“Neither the drug nor the biomarker test is approved for use in this setting at this time, but if I had a patient whose tumor had PD-L1 expression on at least half of the cells and if pembrolizumab was available, I think that I would find the data compelling to look at the drug as the treatment option for that patient,” Garon said.
Among the patients recruited to this trial, 384 had received prior therapies and 101 patients were treatment-naïve. All patients continued to receive pembrolizumab until disease progression, death, withdrawal from the study, or development of intolerable toxicity.
This study was funded by Merck. Garon’s institution received funds to conduct the trial, but he declares no other conflicts of interest.
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