Trials Show Immunotherapies Effective Against Advanced Melanoma

Results from two clinical trials reported at the American Society for Clinical Oncology (ASCO) Annual Meeting 2015 highlighted the potential for immunotherapies nivolumab and pembrolizumab as treatment for advanced melanomas, according to Rene Gonzalez, MD, investigator at the University of Colorado Cancer Center and director of the Melanoma Research Clinics at the CU School of Health, and study.

The immunotherapy combination was considered to be most appropriate for patients whose melanomas do not over express the protein PDL1, which can be targeted by other drugs.

According to the researchers at ASCO, pembrolizumab works by “blocking these T-cell PD1 receptors, thereby disallowing interaction between PDL1 and PD1 and leaving the immune system primed to attack tumor tissue.”

Gonzales commented that in the phase III trial CheckMate 067, the combination of nivolumab with ipilimumab showed "better efficacy but more toxicity,” and proposed that “maybe PDL1-negative patients will benefit most from the combination, whereas PDL1-positive patients could use a drug targeting that protein with equal efficacy and less toxicity.”

During a plenary session at ASCO, results presented from the KEYNOTE-002 clinical trial underscored that not only did pembrolizumab improve survival of patients with metastatic melanoma over the use of chemotherapy alone, but also it does not limit its benefits to patients whose cancers over express the PDL1 protein.

Study results also indicated that in the current trial, of the 179 patients who only received chemotherapy, the disease remained controlled in 16% of patients at 6 months. Whereas, of the 361 patients who received pembrolizumab, 36% remained progression-free at 6 months — essentially more than double the percentage of chemotherapy alone.

Under the FDA Fast Track Development Program in 2014, pembrolizumab was approved for metastatic melanoma treatment that had progressed after being treated with the first-line immune therapy drug ipilimumab and, if BRAF mutant, also a BRAF inhibitor.

Researchers are currently testing pembrolizumab in more than 30 clinical trials for cancers including renal cell carcinoma (KEYNOTE-029), head and neck squamous cell carcinoma (KEYNOTE-055), esophageal carcinoma (KEYNOTE-028), non-small cell lung cancer (KEYNOTE-024), urothelial cancer (KEYNOTE-052 and KEYNOTE-045), and others. Additionally, there are more than 40 trials of nivolumab currently recruiting patients.