Background and importance Dabrafenib/trametinib and vemurafenib/cobimetinib significantly increased progression free survival (PFS) and overall survival (OS) in patients with advanced or metastatic melanoma with BRAF mutations, in phase III clinical trials (CT).
Aim and objectives To assess the effectiveness and safety of vemurafenib/cobimetinib and dabrafenib/trametinib in patients with locally advanced or metastatic melanoma in real life.
Material and methods We performed a retrospective, multicentre, observational study of patients with BRAF mutated melanoma treated with vemurafenib/cobimetinib or dabrafenib/trametinib until 30 September 2020. Variables collected were: sex, age, stage, performance status (PS), previous treatments, duration of treatment and response, dose received and dose adjustments. Variables evaluated were: PFS, OS, adverse events (AE), withdrawal rate and reason for withdrawal.
Results We included 42 patients (27 men, mean age 62.4±15.2 years). 81% had metastatic melanoma and 19% had locally advanced melanoma. 20 patients received vemurafenib/cobimetinib, 13 dabrafenib/trametinib, 1 dabrafenib and 8 received both drugs. 14 patients presented PS=0, 24 PS=1 and 13 PS≥2. 71.4% and 14.3% of patients treated with vemurafenib/cobimetinib and dabrafenib/trametinib, respectively, received the drug as firstline treatment.
Effectiveness and safety variables were evaluated in 38 patients (n=4 loss to follow-up):
median PFS was 9.71 (95% CI 5.77 to NA) and median OS was 18.5 (95% CI 11.9 to NA) in vemurafenib/trametinib treated patients, while in those who received dabrafenib/cobimetinib, median PFS was 10.1 (95% CI 7.7 to NA) and OS was not reached.
median duration of treatment with vemurafenib/cobimetinib and dabrafenib/trametinib was 99 (IR 20–243) and 198 (IR 73–632) days, respectively.
14.8% and 26.3% of patients treated with vemurafenib/cobimetinib and dabrafenib/trametinib, respectively, showed complete response, 33.3% and 26.3% partial response, 11.1% and 15.8% progressed and 33.3% and 15.8% were not assessable (early toxicity or recent onset).
All patients treated with vemurafenib/cobimetinib presented with AE during treatment (85.2% dermatological and 74.1% gastrointestinal) and in 26% treatment was withdrawn. In patients treated with dabrafenib/trametinib, 94.7% showed AE (52.6% dermatological, 68.4% gastrointestinal and 57.9% low grade fever/discomfort), and in 15.8% treatment was withdrawn due to toxicity.
Conclusion and relevance The effectiveness observed in our patients was slightly lower than that seen in the pivotal CT (COBRIM-b) in vemurafenib/cobimetinib patients. In contrast, it was similar to that seen in other pivotal CTs (COMBI-v and COMBI-d) in patients treated with dabrafenib/trametinib.
The toxicity profile of both drugs was similar to the pivotal CTs. Dabrafenib/trametinib was better tolerated than vemurafenib/cobimetinib.
Conflict of interest No conflict of interest
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.