On June 22, 2022, the FDA accelerated the approval of Tafinlar (dabrafenib; from Novartis), a BRAF mutation inhibitor, in combination with Mekinist (trametinib; from GlaxoSmithKline), a MEK inhibitor, for the treatment of unresectable or metastatic solid tumors and BRAF V600E mutation in patients aged 6 years or older who have had disease progression after receiving previous treatment.
“The combination of dabrafenib and trametinib demonstrated meaningful efficacy in multiple BRAF-positive tumor types, including in some patients with rare cancers who have no other treatment options available,” said lead investigator Vivek Subbiah, MD, Medical Director of the Clinical Center for Targeted Therapy, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston.
“Physicians should consider a BRAF test as a routine diagnostic step that could enable a new option for treating patients with many solid tumors,” Dr. Subbiah emphasized.
This approval was based on the results of 3 clinical trials that included 131 adults in the first 2 studies, 36 patients in the pediatric study, and a total of 24 types of solid tumors, including gliomas (a type of brain cancer), biliary tract cancer, adenocarcinoma of the small intestine, gastrointestinal stromal tumor, and anaplastic thyroid cancer.
In these 3 studies, the overall response rate was up to 80% in patients with BRAF V600E solid tumors. The highest overall responses were seen in patients with biliary tract cancer (46%) and in those with low-grade (50%) or high-grade (33%) gliomas. In the 2 studies with 131 adults, 54 patients had a response. In the 36 pediatric patients, the overall response rate was 25%, and the response lasted 6 months or longer in 78% of the patients; in 44% of the patients, the response to treatment lasted 24 months or longer.
The most common side effects with this combination therapy in adults were fever, fatigue, nausea, rash, chills, headache, hemorrhage, cough, vomiting, constipation, diarrhea, myalgia, arthralgia, and edema. In the pediatric patients, the most common side effects were fever, rash, vomiting, fatigue, dry skin, cough, diarrhea, dermatitis acneiform, headache, abdominal pain, nausea, hemorrhage, constipation, and paronychia.