The efficacy of dabrafenib in the treatment of non-small cell lung cancer

Introduction: Dabrafenib is a reversible ATP-competitive kinase inhibitor that targets the MAPK pathway. It was approved on May 29, 2013 for the treatment of melanoma with V600E or V6000K mutations. It is also used to treat metastatic non-small cell lung cancer, anaplastic thyroid cancer, etc. with the same mutations. Dabrafenib combined with trametinib provides an effective treatment option for patients with BRAF V600E mutated non-small cell lung cancer, with a high response rate and durable efficacy, and has been recommended by many authoritative treatment guidelines around the world.

How it works

blocks a key protein molecule called mutated B-raf (B-RAF), a protein that is part of a cell signaling pathway that controls cell growth in many different tissues in the body. Mutations that lock the B-RAF protein in an active state may cause excessive signaling in the RAS/RAF/MEK/ERK (MAPK pathway) signaling pathway. When the activity of mutated B-RAF is blocked, cancer cells stop growing and die.

Efficacy of dabrafenib in the treatment of non-small cell lung cancer

In clinical trials, dabrafenib combined with trametinib showed a high overall response rate in the treatment of patients with BRAF V600E mutated non-small cell lung cancer. According to different studies, the overall response rate R can reach 63.2%-64%. The median progression-free survival (PFS) of dabrafenib combined with trametinib in different studies ranged from 9.7 months to 14.6 months. In addition, long-term follow-up data showed that the 5-year overall survival rates of treated and newly treated patients were 19% and 22% respectively. The global multicenter, open-label Phase II trial CDRB436E2201 confirmed the efficacy of dabrafenib combined with trametinib in first-line and previously treated patients with BRAF V600E-mutant NSCLC.

Adverse reactions

The safety profile of dabrafenib combined with trametinib is consistent with the safety data of other approved indications, indicating that the combination therapy is well tolerated. The most common adverse reactions in adult patients are fever, fatigue, nausea, rash, chills, headache, bleeding, cough, vomiting, constipation, diarrhea, myalgia, arthralgia and edema. The most common adverse reactions in pediatric patients are fever, rash, vomiting, fatigue, dry skin, cough, diarrhea, acneiform dermatitis, headache, abdominal pain, nausea, bleeding, constipation and paronychia.