NEW YORK -- Pooled analysis from three studies suggests there may be a survival advantage for advanced non-small cell lung cancer patients who lack PD-L1 expression and receive pembrolizumab (Merck's Keytruda) and chemotherapy as a front-line option.
At the International Association for the Study of Lung Cancer this week, Merck presented combined analysis of the KEYNOTE-189, KEYNOTE-407, and KEYNOTE-021 studies, which randomized patients to receiving either first-line pembrolizumab and chemotherapy or just chemotherapy, and included around 430 advanced NSCLC patients who had a PD-L1 tumor proportion score of less than 1 percent. In the studies, patients with EGFR or ALK alterations were excluded.
The US Food and Drug Administration has already approved pembrolizumab as a first-line treatment option in combination with chemotherapy in NSCLC, regardless of PD-L1 status. The agency approved the drug for this indication based on data from the KEYNOTE-021 study, which analyzed outcomes according to PD-L1 status but the cohort was small, involving only around 123 patients. The latest pooled data provides more evidence that the drug combination extends survival regardless of PD-L1 status.
"The goal of our robust lung cancer clinical development program has always been to extend survival for patients who are diagnosed with this deadly and aggressive disease," Jonathan Cheng, VP of oncology clinical research at Merck Research Laboratories, said in a statement. "In this pooled analysis of three randomized KEYNOTE studies in advanced non-small cell lung cancer, [pembrolizumab] in combination with chemotherapy demonstrated an improvement in overall survival compared to chemotherapy alone among newly diagnosed patients whose tumors do not express PD-L1."
In the study, at a median follow up of around 10 months, the combination of pembrolizumab and chemotherapy reduced the risk of death by 44 percent compared to chemotherapy alone. Median overall survival was 19 months in the pembrolizumab containing arm versus 11 months in the comparator arm, and median progression-free survival was 6.5 months versus 5.4, respectively. Nearly 47 percent of those receiving the combination regimen saw their tumors shrink and 42 percent responded to the drug for a year or longer. Meanwhile, among those receiving just chemotherapy, nearly 29 percent saw their tumors shrink and 35 percent responded for a year or longer.
Of the patients who received pembrolizumab plus chemotherapy, 68 percent had a serious adverse event versus 72 percent of those treated with just chemotherapy. Grade 3 to grade 5 adverse events were attributed to 9 percent of deaths in the combination arm compared to 6 percent of deaths in the comparator arm.