The Food and Drug Administration (FDA) has approved Tafinlar® (dabrafenib) with Mekinist® (trametinib) for the treatment of pediatric patients 1 year of age and older with low-grade glioma with a BRAF V600E mutation who require systemic therapy.
The approval was based on data from the phase 2/3 TADPOLE trial (ClinicalTrials.gov Identifier: NCT02684058), which investigated the combination in pediatric patients 1 to less than 18 years of age with BRAF V600E mutation-positive low-grade glioma (WHO grades 1 and 2) who 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 efficacy outcome measures.
Findings showed a statistically significant improvement in ORR among patients treated with D+T compared with those who received C+V (46.6% [95% CI, 34.8-58.6] vs 10.8% [95% CI, 3.0-25.4]; P <.001). At a median follow-up of 18.9 months, median PFS was 20.1 months (95% CI, 12.8, not estimable) with D+T and 7.4 months (95% CI, 3.6-11.8) with C+V (hazard ratio, 0.31 [95% CI, 0.17-0.55]; P <.001).The median duration of response was 23.7 months (95% CI, 14.5, not estimable) in the D+T arm and not estimable (95% CI, 6.6, not estimable) in the C+V arm.
Overall survival results did not reach statistical significance at interim analysis, which was conducted when all patients 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 also approved Tafinlar tablets for oral suspension and Mekinist for oral solution.
Commenting on the approval, Reshema Kemps-Polanco, Executive Vice President, US Oncology at Novartis, said: “This new indication for Tafinlar + Mekinist is a potential new standard of care treatment option for young patients with this form of brain cancer with a BRAF V600E mutation, in formulations specifically designed for them.”
- 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.