The US Food and Drug Administration (FDA) announced accelerated approval for the combination of 2 therapies, dabrafenib and trametinib, for the treatment of unresectable or metastatic solid tumors with BRAF V600E mutations, including gastrointestinal stromal tumors (GISTs).

The approval applies to use in adults and children aged 6 years and above who have progressed despite prior treatment and have no satisfactory alternative treatment options.

“On June 22, 2022, the [FDA] granted accelerated approval to dabrafenib (Tafinlar, Novartis) in combination with trametinib (Mekinist, Novartis) for the treatment of adult and pediatric patients ≥6 years of age with unresectable or metastatic solid tumors with BRAF V600E mutation who have progressed following prior treatment and have no satisfactory alternative treatment options,” according to the news release.


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The approval was based on data from multiple clinical trials including BRF117019 (NCT02034110), NCI-MATCH (NCT02465060), CTMT212X2101 (NCT02124772), COMBI-d, COMBI-v, and BRF113928. The BRF117019 and NCI-MATCH studies evaluated 131 adult patients and found that 54 (41%) experienced an objective response using standard response criteria. The patients had 24 different types of tumors, including GIST.

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Thirty-six pediatric patients were enrolled in parts C and D of the CTMT212X2101 trial. The overall response rate of these patients was 25%. The duration of response was ≥6 months in 78% of patients and ≥24 months in 44% of patients.

The most commonly experienced (≥20%) adverse reactions during the adult trials included pyrexia, fatigue, nausea, rash, chills, headache, hemorrhage, cough, constipation, diarrhea, myalgia, arthralgia, and edema.

In the pediatric trials, the most common reactions included pyrexia, rash, vomiting, fatigue, dry skin, cough, diarrhea, dermatitis acneiform, headache, abdominal pain, nausea, hemorrhage, constipation, and paronychia.

Due to known intrinsic resistance to BRAF inhibition, the combined usage of the 2 drugs is not indicated for patients with colorectal cancer. In addition, the use of dabrafenib is not indicated for any wild-type BRAF solid tumors.

Reference

FDA grants accelerated approval to dabrafenib in combination with trametinib for unresectable or metastatic solid tumors with BRAF V600E mutation. News release. US Food and Drug Administration (FDA); June 23, 2022.