Dabrafenib and trametinib can be used in combination to treat patients with advanced skin cancer, also known as melanoma.
Approximately 40% of patients with advanced melanoma possess what is known as activating BRAF mutations in their tumours. This culminates in the constant signaling of the mitogen-activated protein kinase (MAPK) pathway. The inhibition of this pathway is done by concentrating on MEK as well as BRAF-mutant proteins. This activity involves the drug dabrafenib being used in tandem with trametinib and this results in progression free survival, improved response, and greater chances of survival of the patients with BRAF mutation versus those with BRAF inhibitor monotherapy.
The study, ‘Factors predictive of response, disease progression, and overall survival after dabrafenib and trametinib combination treatment: a pooled analysis of individual patient data from randomized trials’ was done with the objective of recognizing clinical factors which share a relationship with survival and long-term response. This is based on the use of collected data from randomized trials in patients experiencing BRAF-mutant melanoma who are being treated with dabrafenib and trametinib.
The design of the experiment involved a retrospective individual data analysis. The randomized trials used had the credibility of being published and this encompassed treatment of patients with BRAF mutant metastatic melanoma who were taking 150 mg of dabrafenib two times per day plus 2 mg of trametinib daily. The data was combined from affected individuals in BRF113220 (part C; March 26, 2010, to Jan 15, 2015), COMBI-d (May 4, 2012, to Jan 12, 2015), and COMBI-v (June 4, 2012, to March 13, 2015) randomized trials. Excluded from participating in the trial were patients with brain metastases that had not been treated. Baseline factors were viewed and analyzed with regards to their relationship with progression-free survival and overall survival. Multivariate and univariate analyses were employed as well as regression tree analyses.
There were 617 patients involved: 396 of them experienced progression events (death or disease worsening) and 290 died. The rate one-year progression-free survival was 48%, however, the overall rate of survival was 74%. The two-year progression-free survival rate was 30% while the overall survival rate was 53%. The data achieved was consistent with trials of individuals. It was found that survival after progression for patients with disease progression at baseline was the longest in those with progression at baseline and shortest in those with concurrent progression at baseline.
In conclusion, the study provides a foundation for the assessment of therapeutic development of advanced melanoma and to recognize those who are in need of better treatment options. Furthermore, patients have long-term disease control when dabrafenib is used in tandem with trametinib. Studies of this nature are incredibly crucial to results of melanoma in patients.
Written By: Tarique Plummer, BSc Hons Biochemistry & Biotechnology