New data from a Phase 1 clinical trial revealed that the immunotherapy drug pembrolizumab (Keytruda) may have a higher efficacy in melanoma treatment than conventional chemotherapy agents. The findings were published in The Journal of The American Medical Association, in the study “Association of Pembrolizumab With Tumor Response and Survival Among Patients With Advanced Melanoma.”
Pembrolizumab is a therapeutic antibody that blocks the programmed cell death 1 receptor (PD-1), expressed by cells from the immune system. PD-1 is responsible for inhibiting the immune response to cancer cells, avoiding exacerbated immune reactions. Pembrolizumab releases immune cells from PD-1 inhibitory functions, allowing them to target and destroy the cancer cells.
“The early data from this research showed the unprecedented activity of pembrolizumab in people with advanced melanoma, and we can now report the full results of the study,” Dr. Antoni Ribas, the study’s first author, a professor of hematology and oncology at the University of California, Los Angeles (UCLA), and director of the UCLA Jonsson Comprehensive Cancer Center Tumor Immunology Program, said in a press release.
UCLA researchers analyzed data from 655 patients with advanced or metastatic melanoma from Australia, Canada, France and the U.S, who were given three dosing regimens of pembrolizumab: 10 mg/kg every 2 weeks, 10 mg/kg every three weeks, or 2 mg/kg every three weeks.
Data from a long-term follow-up of the Phase 1 trial revealed no differences among the dosing regimens, with pembrolizumab administration inducing an objective tumor regression in 33 percent of the patients. The vast majority of patients had long-term responses, with 74 percent continuing to respond after one year and after three years.
Investigators also compared the outcomes of patients who had received prior treatment with ipilimumab (a CTL-4 inhibitor that also turns off the inhibitory mechanism of the immune system) versus untreated patients, finding that the objective tumor regression increased to 45 percent in advanced melanoma patients who had not been previously treated.
They also demonstrated that pembrolizumab had a higher progression-free survival rate and was better tolerated, compared to chemotherapy. Furthermore, when compared to ipilimimab, another immunotherapy drug, pembrolizumab significantly improved overall survival and had lower toxicity rates.
The study’s results led to the approval of pembrolizumab by the Food and Drug Administration (FDA) as an initial treatment of unresectable or metastatic melanoma in December 2015 .