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Triple-Drug Therapy Under Study in BRAF-Mutant Melanoma

By: Dana A. Elya, MS, RD, CDN
Posted: Thursday, August 29, 2019

A novel triple-drug combination under study for patients with melanoma containing the gene BRAF V600E appeared to be effective, with “long-lasting anti-tumor responses.” The combination consists of the BRAF inhibitors dabrafenib and trametinib along with the immune checkpoint inhibitor pembrolizumab. The study, conducted by Antoni Ribas, MD, PhD, of the University of California, Los Angeles, and colleagues, was published in Nature Medicine.

“Earlier attempts to combine a targeted agent with an immune checkpoint inhibitor as a double-combination therapy had debilitating side effects for patients, and it was just too toxic to continue testing, so we went back to the drawing board,” said Dr Ribas in a UCLA Health press release. “We found that by using two targeted inhibitors, instead of just one, in combination with a checkpoint inhibitor, we could safely and effectively treat the cancer.”

The phase I trial started with 15 patients—all with stage IV metastatic melanoma. With the combination therapy, target lesions were reduced in diameter, compared with baseline, in 14 patients. A complete or partial response to therapy was observed in 11 patients (73%), the tumors did not grow again for between 12 and 27 months. The average progression-free survival for all patients was 15.4 months.

Once the dosing regimen was identified, and the maximum tolerated dose was established, the study moved to part 3 with a phase II randomized trial.

“With this triple combination, we’re doing two things at once: using the two inhibitors to block the cancer from spreading and stimulating the immune system. Enlisting an immune response to the cancer is aimed at having more durable responses to the therapy,” shared Dr Ribas in the UCLA Health press release.

Disclosure: The study authors’ disclosure information may be found at nature.com.



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