Evaluating the long-term outcomes of encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF-mutated advanced melanoma.

This study reported the long-term effectiveness and safety of encorafenib (Braftovi) alone or in combination with binimetinib (Mektovi) or vemurafenib (Zelboraf) alone in patients with BRAF-mutated advanced melanoma. The data showed that the encorafenib plus binimetinib combination lead to long-term effectiveness and no new safety issues in these patients.

Melanoma is an aggressive form of skin cancer. It is often caused by specific gene mutations (abnormalities). BRAF and MEK are the most common mutated genes in melanoma. These mutations allow tumors to grow at a rapid rate. Using drugs that target these mutations can slow disease progression and improve survival. BRAF inhibitors and MEK inhibitors are used to treat these tumors.

Vemurafenib is an approved targeted therapy for BRAF-mutant melanoma. Encorafenib is another drug that targets BRAF-mutant cancer cells. Binimetinib is a drug that blocks MEK. It has been shown that encorafenib combined with binimetinib improved survival outcomes in patients with advanced melanoma with BRAF mutations. However, the long-term effectiveness and safety outcome of this combination compared to vemurafenib or encorafenib alone remain under investigation.

This study involved 577 patients with BRAF-mutated advanced melanoma. Patients were randomly assigned into three groups. Group 1 included 192 patients who received encorafenib plus binimetinib combination. Group 2 included 191 patients who received vemurafenib alone. Group 3 included 194 patients who received encorafenib alone. The average follow-up time was 70.4 months.

The average survival without cancer worsening was 14.9 months in group 1 compared to 7.3 months in group 2 and 9.6 months in group 3. After 5 years, 23% of the patients in group 1 were alive without cancer worsening compared to 10% of patients in group 2 and 19% of patients in group 3.

The average overall survival was 33.6 months in group 1 compared to 16.9 months in group 2 and 23.5 months in group 3. After 5 years, 35% of the patients in group 1 were alive compared to 21% of patients in group 2 and 35% of patients in group 3.

The average time taken to respond to treatment was 18.6 months in group 1 versus 12.3 months in group 2, and 15.5 months in group 3. 92.2% of the patients in group 1 achieved disease control (cancer shrunk or remained stable) versus 81.2% of the patients in group 2, and 84% of patients in group 3.

Serious side effects occurred in 70% of patients in groups 1 and 3 and 66% of those in group 2. 

This study concluded that the encorafenib plus binimetinib combination lead to long-term benefits and no new safety issues in patients with BRAF-mutated advanced melanoma.

This study was funded by Array BioPharma (Pfizer), the manufacturer of encorafenib and binimetinib.