PHILADELPHIA — At the AACR Annual Meeting 2015, immunotherapies, called PD-1 inhibitors, were front and center stage, due to clinical trial results that led to U.S. Food and Drug Administration (FDA) approvals for treating melanoma and non-small cell lung cancer (NSCLC).
In particular, PD-1 inhibitor pembrolizumab (Keytruda; Merck) demonstrated positive results.
Currently, ipilimumab (Yervoy; Bristol-Myers Squibb) is the standard of care for first-line therapy for patients with metastatic melanoma — and pembrolizumab (Keytruda) is approved as second-line therapy for patients with metastatic melanoma whose tumors no longer respond to ipilimumab.
But in the KEYNOTE-006 phase 3 clinical trial, which compared two FDA-approved immune checkpoint inhibitors as first-line therapy for patients with advanced melanoma, pembrolizumab yielded significantly better treatment outcomes than ipilimumab (Yervoy) for all endpoints studied.
“This is the first clinical trial to compare head-to-head two immune checkpoint inhibitors as front-line therapy for melanoma,” said Antoni Ribas, MD, PhD, professor of hematology and oncology, and director of the Tumor Immunology Program Area at UCLA Jonsson Comprehensive Cancer Center.
“We think these data should change the paradigm of treatment for these patients,” said Ribas, who presented the results at AACR. The clinical trial results were recently published in The New England Journal of Medicine.
Researchers randomly assigned 834 patients with metastatic melanoma, 66 percent of whom had not previously received therapy, and 79 percent of whom had tumors that had the PD-L1 protein to the following treatment schedules: 10 mg/kg pembrolizumab every 2 weeks, 10 mg/kg pembrolizumab every 3 weeks, or four doses of 3 mg/kg ipilimumab every 3 weeks. They assessed treatment responses after 12 weeks and every 6 weeks thereafter.
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Six months after treatment, estimated progression-free survival (PFS) rates were 47.3% for pembrolizumab every 2 weeks, 46.4% for pembrolizumab every 3 weeks, and 26.5% for ipilimumab. Median estimates of PFS were 5.5 months, 4.1 months, and 2.8 months respectively. After 12 months, estimated overall survivals (OS) rates were 74.1%, 68.4%, and 58.2% respectively. The overall response rate for the pembrolizumab group was 33%, compared with 12% for the ipilimumab group, and fewer patients in the pembrolizumab group experienced side effects (12%) compared with the ipilimumab group (20%).
“These results meet and exceed the baseline assumptions of the benefit of pembrolizumab over ipilimumab,” Ribas said, adding that he hopes drug regulatory agencies act quickly on approving pembrolizumab for front-line therapy for metastatic melanoma.
Non-small cell lung cancer advances
Pembrolizumab (Keytruda) also showed improved overall survival in lung cancer patients treated with the inhibitor.
Edward B. Garon, MD, associate professor of medicine at the David Geffen School of Medicine at the University of California, Los Angeles, presented data from the phase 1 KEYNOTE-001 clinical trial, in which pembrolizumab’s safety and efficacy are being evaluated as a treatment for non-small cell lung cancer (NSCLC).
The trial looked at 495 patients treated with pembrolizumab. The overall response rate was 19 percent. But for patients with high levels of PD-L1 expression, 45 percent responded to the drug. Garon said this benefit “substantially exceeds that expected from chemo” in patients with high levels of PD-L1 expression.
Merck announced Sunday that it has submitted the data to the FDA for review.