Background The BRAF inhibitor dabrafenib and the MEK inhibitor trametinib are indicated for the treatment of patients with unresectable or metastatic melanoma with a BRAF (V600) mutation. The combination of both drugs has shown more effectiveness and an increase in survival. These are used in first-line treatment for patients with mutated BRAF, and in the second line for patients with no-mutated BRAF.
Purpose To evaluate the effectiveness and tolerability of both dabrafenib and trametinib, based on the overall survival (OS) and progression-free survival (PFS) for metastatic melanoma.
Material and methods Retrospective study that included patients receiving a combination of dabrafenib and trametinib. The period of study was from May 2015 until 30 September 2018 (end of study). The required data was obtained from clinical electronic history Cerner Millennium and the variables were: gender, age, wild or mutated BRAF, dose reductions, start date, adverse effects, progression and death date.
The Kaplan–Meier method was used to analyse PFS and OS. Statistical analysis was made with STATA.14.
Results There were 14 men and 18 women receiving the combination. Median age was 59.4 years (range 34.4–82.7) and V600-BRAF was mutated in all patients.
Most of the patients left the treatment, and only six are still receiving it. Patients that discontinued the treatment were 25 due to progression and two due to adverse effects. The median PFS is 7.38 months (95% CI: 5.51 to 11.44). During the study, 13 patients died. The median OS is 16.23 months (95% CI: 14.52 to not reached).
Many adverse effects appeared with this combination and 38% of the patients had to reduce dose due to toxicity. Most common side effects were: fever, dermatologic effects (such as eczema, rash, oedemas), neurological toxicity (such as cephalea, confusion, dizziness, loss of memory), visual alterations (photophobia, visual reduction) and asthaenia.
Conclusion Dabrafenib and trametinib are a good alternative for patients diagnosed with metastatic melanoma with BRAF mutation. Despite the toxicity, this is a serious conditioning for patients’ life, and the results of PFS and OS are significant for patients without other options for years. More studies comparing dabrafenib and trametinib with other therapies in advanced melanoma, such as immunotherapy, are required to choose the best option for treating patients.
References and/or acknowledgements No conflict of interest.