Melanoma survival improves with targeted combo therapies

Recent studies appear to confirm greater efficacy of combination treatments over vemurafenib monotherapy in improving progression-free survival for patients with melanoma.

According to data presented at the European Society for Medical Oncology 2014 Congress in Madrid, Spain, patients with melanoma who received the BRAF inhibitor vemurafenib along with the MEK inhibitor cobimetinib demonstrated a better response rate and greater progression-free survival compared to patients who received only vemurafenib.

The phase 3 CoBRIM study included 495 treatment-naïve patients who had BRAFV600-mutation-positive unresectable locally advanced melanoma or metastatic melanoma. Study participants were randomized to receive vemurafenib 960 mg twice-daily for 28 days and either cobimetinib or placebo for (60 mg daily from days one to 21). The primary endpoint was progression-free survival.

Patients who received combination therapy demonstrated “significantly improved” median progression-free survival at 9.9 months, compared to 6.2 months for patients in the placebo arm. There was a response rate of 68 percent for those receiving combination therapy, compared to 45 percent for the control arm. Complete response was 10 percent for those given combination treatment, compared to 4 percent for those who were given only vemurafenib.

There were more grade 3 and higher adverse events among patients receiving combination therapy than among those receiving only vemurafenib. The combination therapy did, however, appear to reduce the incidence of skin-related side effects from vemurafenib, according to the news release.

“We anticipate that the combination of a BRAF and MEK inhibitor will become a new standard treatment for advanced BRAF-mutant melanoma,” Grant McArthur, M.B.B.S., Ph.D., lead study author and head of the Cancer Therapeutics Program at Peter MacCallum Centre, Melbourne, Australia, said in the news release. “The data lay the foundation for the addition of treatments either in sequence or in further combination to obtain even better results.”

Next: Study examines dabrafenib with trametinib

A second study, also presented at the ESMO Congress, showed that a treatment combination of dabrafenib and trametinib allowed for longer overall survival and progression-free survival plus better response rates for patients with melanoma compared to those treated only with vemurafenib.

The open-label phase 3, two-arm study included 704 patients with advanced BRAFV600E/K mutation-positive melanoma who were randomized to receive either a combination of 150 mg twice-daily dabrafenib and 2 mg once-daily trametinib or to 960 mg twice-daily vemurafenib alone. Primary endpoint was overall survival, and secondary endpoints were progression-free survival, duration of response, objective response rate and safety, according to the news release.

During a preplanned interim analysis, study investigators found a 31 percent improvement in overall survival among patients receiving combination therapy and a reduction of risk of disease progression of 44 percent. Median progression-free survival was 11.4 months for the combination therapy compared to 7.3 months for vemurafenib alone. The study was stopped in July, and patients who had been randomized to receive only vemurafenib were allowed to switch to the combination therapy.

Rates of severe adverse events were similar in both arms of the study, but combination therapy demonstrated a lower rate of cutaneous squamous cell carcinoma, investigators reported.

“Of special relevance is the lower risk for new cutaneous malignancies, which might be a surrogate for other secondary malignancies associated with the use of monotherapy BRAF inhibitors,” Reinhard Dummer, M.D., faculty coordinator for melanoma at ESMO, said in the news release.

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