Dabrafenib combined with trametinib is an efficient treatment option for metastatic melanoma

This review examined the safety and effectiveness of dabrafenib (Tafinlar) and trametinib (Mekinist) for inoperable metastatic melanoma. Researchers concluded that this combined treatment is an important therapy option for patients with metastatic melanoma. 

Some melanoma patients have a mutation (permanent change) in the BRAF gene. BRAF inhibitors (such as dabrafenib) are used to treat these tumors. Over time, patients can become resistant to this treatment. This resistance happens due to the reactivation of a certain protein (MAPK) that allows for tumor growth. Adding an MAPK inhibitor to the treatment (such as trametinib) could help to overcome BRAF resistance. 

This review analyzed the safety and effectiveness of dabrafenib combined with trametinib in patients with inoperable metastatic (spread to other parts of the body) BRAF-mutated melanoma.

In one study, treatment with dabrafenib and trematinib reduced the risk of disease progression or death by 25% compared to dabrafenib alone. Combined treatment also reduced the risk of a shorter overall survival (time from treatment until death from any cause) by 29%. 16% of patients receiving the combined treatment had a complete response (tumor disappearance) at 11 months, compared to 13% for dabrafenib alone. Health-related quality of life was also higher in patients treated with the combined therapy.

Combined treatment was also significantly more effective in patients with BRAF mutations. Patients receiving the combined treatment had a 61% lower risk of shorter time to progression compared to those treated with dabrafenib alone. The combined treatment was also found to be more effective than treatment with vemurafenib (Zelboraf, a chemotherapy) alone.

In a different study, the combined treatment was not effective in patients who did not previously respond to dabrafenib.

The combined treatment was not associated with an increase of overall negative side effects (87% of patients) compared with dabrafenib alone (90%). The majority of side effects were of moderate severity. The most common side effect with combined treatment was fever. Hand-foot syndrome (swelling and pain in the hands and feet), a thickening of the skin and alopecia (hair loss) were also reported. 32% of patients treated with combined therapy and 31% treated with dabrafenib alone had severe effects. Fever was the most frequent in both cases. 

This review suggested that dabrafenib plus trametinib was more effective than dabrafenib alone. The combination was not associated with an increase in negative side effects.