A recent study titled “Combined Vemurafenib and Cobimetinib in BRAF-Mutated Melanoma”, and presented at the 2014 European Society for Medical Oncology (ESMO) conference in Madrid, Spain, showed that patients with advanced melanoma could benefit from combination therapy of Zelboraf (vemurafenib) with the experimental drug cobimetinib.
The study, published in The New England Journal of Medicine, showed that the BRAF mutation present in melanoma cells could provide the necessary signal to trigger uncontrolled proliferation in these tumors
It had been previously shown that combining BRAF and MEK inhibitors could improve clinical outcomes in patients suffering from melanoma by preventing or delaying the onset of resistance observed with BRAF inhibitors alone. However, a serious side effect of a secondary cancer had developed in 25% of patients who had received Zelboraf alone.
“We wondered why it was that we were getting the melanoma to shrink, but another skin cancer was developing. Now we’ve demonstrated the significantly increased duration of response to the therapy”, co-author of the study Dr. Antoni Ribas, UCLA professor of medicine (hematology and oncology) and Jonsson Comprehensive Cancer Center member said in a Pasadena Independent interview.
Based on these previous results, the team designed a phase 3 study to assess the efficacy of combining Zelboraf (BRAF inhibitor) with cobimetinib (MEK inhibitor) in the treatment and progression-free survival of 495 patients with previously untreated unresectable locally advanced or metastatic BRAF V600 mutation–positive melanoma.
Of the 70,000 new cases of melanoma diagnosed each year in the U.S., around 50% carry the BRAF mutation. These patients can receive Zelboraf treatment alone, since this drug has received a U.S. Food and Drug Administration approval back in 2011.
Data was collected over a one-year period and included 495 patients from 135 sites in the United States, Australia, New Zealand and Europe.
The results demonstrated that the median progression-free survival was 9.9 months in the combination group and 6.2 months in the control group (Zelboraf and placebo). The combination therapy group had a significantly higher complete or partial response rate (68%) compared to the control group (45%), along with higher 9-month survival rates (81% vs 73%).
Some toxic side effects were verified in 20% of patients receiving the combination therapy, such as diarrhea, rash, fatigue and edema.
However, combining Zelboraf and cobimetinib decreased the number of secondary cutaneous cancers.
Researchers now hope these promising results will grant the combination therapy of Zelboraf and cobimetinib an FDA approval for the treatment of patients suffering with BRAF mutated metastatic melanoma.