曲美替尼联合达拉非尼治疗1岁及以上低级别胶质瘤儿童患者

Indications for treatment with trametinib combined with dabrafenib

Trametinib combined with dabrafenib can be used to treat pediatric patients 1 year old and above with BRAF V600E mutated low-grade glioma (LGG) who require systemic therapy. It was approved by the US FDA on March 16, 2023. LGG is the most common pediatric brain cancer. BRAF V600 mutations are present in 15-20% of pediatric LGG and are associated with poor survival outcomes and poor response to chemotherapy. Trametinib combined with dabrafenib is the first combination targeted therapy approved for the treatment of pediatric patients with BRAF V600E LGG.

The FDA's approval of Tafinlar + Mekinist (combined with dabrafenib) was based on the results of the phase 2/3 clinical trial TADPOLE, which showed a statistically significant improvement in the overall response rate (ORR) of patients randomized to receive trametinib combined with dabrafenib, which was 47%, compared with 11% for patients randomized to receive chemotherapy. During a median follow-up period of 18.9 months, the median progression-free survival (PFS) in the trametinib plus dabrafenib group was 20.1 months, compared with 7.4 months in the chemotherapy group.

In addition, 86% of patients in the trametinib combination treatment group had tumor size reduced or remained stable, compared with 46% of patients in the chemotherapy group. Quality of life was better in the trametinib plus dabrafenib group at all time points. The study results of Tafinlar+Mekinist in the treatment of pediatric patients with relapsed or refractory BRAF V600 high-grade glioma (HGG) showed that the ORR of trametinib combined with dabrafenib was 56.1%.

The combination of trametinib and dabrafenib helps slow tumor growth by blocking signaling associated with the BRAF and MEK kinases involved in the growth of various types of cancer. The combination therapy of trametinib and dabrafenib has been approved by the FDA for the treatment of multiple BRAF V600 solid tumors, including melanoma, thyroid cancer, and lung cancer.

Dabrafenib is a targeted therapy BRAF kinase inhibitor that targets these altered BRAF proteins and may slow cancer growth. Trametinib is a reversible inhibitor of the kinase activity of mitogen-activated extracellular signal-regulated kinase 1 (MEK1) and MEK2. By inhibiting MEK, it can inhibit the growth of BRAF V600 mutation-positive cancer cells. Trametinib combined with dabrafenib has significant effects in the treatment of multiple cancer types. It is recommended that patients follow the doctor's instructions and receive symptomatic treatment.

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