The US Food and Drug Administration (FDA) has approved Tafinlar (dabrafenib) with Mekinist (trametinib) for the treatment of pediatric patients 1 year of age and older who have low-grade glioma with a BRAF V600E mutation and require systemic therapy.
The approval was based on data from the phase 2/3 TADPOLE trial (ClinicalTrials.gov Identifier: NCT02684058), which was designed to test the combination in pediatric patients aged 1-17 years who had BRAF V600E mutation-positive grade 1-2 glioma and required first systemic therapy.
Study participants were randomly assigned 2:1 to dabrafenib plus trametinib (D+T; n=73) or carboplatin plus vincristine (C+V; n=37). The primary endpoint was overall response rate (ORR). Progression free survival (PFS) and overall survival were additional endpoints.
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There was a significant improvement in ORR among patients treated with D+T compared with those who received C+V (46.6% vs 10.8%; P <.001). The median duration of response was 23.7 months in the D+T arm and not estimable in the C+V arm.
At a median follow-up of 18.9 months, the median PFS was 20.1 months with D+T and 7.4 months with C+V (hazard ratio, 0.31 [95% CI, 0.17-0.55]; P <.001).
Overall survival results did not reach statistical significance at the interim analysis, which was conducted when all patients had completed at least 32 weeks of treatment or had discontinued earlier. There was 1 death reported in the C+V arm.
The most common adverse reactions reported with D+T in this study were pyrexia, rash, headache, vomiting, musculoskeletal pain, fatigue, diarrhea, dry skin, nausea, hemorrhage, abdominal pain and dermatitis acneiform. Grade 3 or 4 laboratory abnormalities included decreased neutrophil count, increased alanine aminotransferase, and increased aspartate aminotransferase.
To ease administration for younger patients, the FDA approved Tafinlar tablets for oral suspension and Mekinist for oral solution.
References
Novartis Tafinlar + Mekinist approved by FDA for pediatric patients with BRAF V600E low-grade glioma, the most common pediatric brain cancer. News release. Novartis. March 16, 2023. https://www.globenewswire.com/news-release/2023/03/16/2629247/0/en/Novartis-Tafinlar-Mekinist-approved-by-FDA-for-pediatric-patients-with-BRAF-V600E-low-grade-glioma-the-most-common-pediatric-brain-cancer.html.
Tafinlar. Package insert. Novartis; 2023. Accessed March 17, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/202806s025lbl.pdf.
Mekinist. Package insert. Novartis; 2023. Accessed March 17, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/204114s025lbl.pdf.
This article originally appeared on MPR
