Atezolizumab, cobimetinib and vemurafenib: a combination for the treatment of BRAF-mutated melanoma

This study investigated atezolizumab (Tecentriq) in combination with cobimetinib (Cotellic) and vemurafenib (Zelboraf) in BRAF-mutated melanoma. They found that this combination is promising and well tolerated in these patients. 

Melanoma or skin cancer is often by specific gene mutations. The most common mutations affect the BRAF and MEK genes. These mutations allow cancer cells to grow at a rapid rate. Suppressing these gene mutations can slow disease progression. Patients with melanoma are treated with BRAF and MEK inhibitors as standard. Vemurafenib (VMF) is BRAF inhibtor. Cobimetinib (CBM) is a MEK inhibitor. 

Some studies also suggest that BRAF/MEK mutations may suppress normal immune function. Cancer cells can evade detection by the immune system via a chemical called PD-L1. Atezolizumab (ATZ) is a drug that blocks PD-L1 activity. Some studies suggest that ATZ may be effective in treating melanoma. It is unclear if combined treatment with ATZ, CBM, and VMF is safe in melanoma.

This study included 39 patients with advanced BRAF-mutated melanoma. This was the second phase of the main study. All patients were given ATZ, CBM, and VMF. Patients were grouped according to whether or not they had previous ATZ treatment. Patients were followed up for an average of 51.8 months.

All patients experienced at least 1 side effect from the treatment. Some of the most common were joint pain, diarrhea, fatigue, swelling, and nausea. Moderate-severe side effects were reported in 66.7% of patients. 33.3% of these were attributed to ATZ. 48.7% were attributed to CBM or VMF. Serious side effects were reported in 41% of patients. 3 patients died during the trial. This was not considered related to treatment. 

71.8% of patients had a confirmed response. The average duration of response was 17.4 months.

The authors concluded that ATZ/CBM/VMF combination is well tolerated and promising in melanoma patients.

This was a small phase 2 trial. A phase 3 trial is ongoing. This study was funded by F. Hoffman-La Roche Ltd., the manufacturer of ATZ, CBM, and VMF.