In a nutshell
This study reported the long-term effectiveness and safety of the combined treatment of vemurafenib (Zelboraf) and cobimetinib (Cotellic) in patients with previously untreated BRAF-mutated advanced melanoma. The data showed that the combination was safe and effective over the long term.
Melanoma is an aggressive form of skin cancer that 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 and MEK inhibitors are used to treat these tumors.
Vemurafenib is a drug that targets BRAF-mutant cancer cells. Cobimetinib is a drug that inhibits MEK. It has been shown that vemurafenib combined with cobimetinib improved survival outcomes in patients with advanced melanoma with BRAF mutations. However, the long-term effectiveness and safety outcome of this combination remains under investigation.
Methods & findings
This study involved 495 patients with previously untreated BRAF-mutated advanced melanoma. Patients were randomly assigned into 2 groups. Group 1 included 247 patients who received vemurafenib plus cobimetinib combination. Group 2 included 248 patients who received vemurafenib plus placebo. The average follow-up time for group 1 was 21.2 months and 16.6 months for group 2.
The average overall survival was 22.5 months for group 1 and 17.4 months for group 2. After 5 years, 31% of the patients in group 1 were alive compared to 26% of patients in group 2.
The average survival without cancer worsening was 12.6 months for group 1 and 7.2 months for group 2. After 5 years, 14% of the patients in group 1 were alive without cancer worsening compared to 10% of patients in group 2.
In the combination group, patients with normal lactate dehydrogenase (LDH; a blood test that measures damage in tissues in the body) at the beginning of the study and those who achieved a complete response to treatment had better overall survival.
Overall, the combined treatment was tolerable and manageable. The most common side effects of the vemurafenib plus cobimetinib combination were pneumonia and an increase in liver enzymes (liver damage).
The bottom line
This study concluded that vemurafenib plus cobimetinib combination leads to long-term benefits and no new safety issues in patients with BRAF-mutated advanced melanoma.
The fine print
This study was funded by F Hoffmann-La Roche-Genentech, the manufacturers of vemurafenib and cobimetinib.
Published By :
Clinical Cancer Research
Jun 22, 2021