Vemurafenib for Pediatric Patients With Tumors Harboring BRAF V600 Mutations

While there was a low accrual rate resulting in an early termination and limited study results, a phase 2 study found the response with vemurafenib among children and young adult patients with tumors harboring BRAF-V600 mutations demonstrated potential benefit.

Vemurafenib, a selective oral inhibitor of the oncogenic BRAF V600 mutated kinase, is FDA-approved for the treatment of metastatic melanoma with BRAF-V600E mutations. Though, as Marie V Nelson, MD, Children’s National Hospital, Washington, DC and coauthors point out, “not all BRAF mutations appear to be the primary driver of tumor progression.” This arm of the MATCH trial aimed to evaluate the response rate to vemurafenib among pediatric patients with BRAF-V600E mutations, excluding patients with low grade glioma as there is previous data demonstrating response to BRAF inhibitors in that population.

There were 22 patients who were matched to the study, however less than 20% of those patients enrolled on the subprotocol. Patients were excluded primary because of ineligible diagnosis of low-grade glioma (n = 7), previous therapy with a BRAF inhibitor (n = 7), or other reasons (n = 4) including not meeting eligibility criteria based on performance status or platelet count.

Overall, patients who did receive vemurafenib tolerated it well, with a majority of adverse event being grade ≤2. There was 1 patient who discontinued therapy due to grade 3 hyperglycemia. There was 1 patient with high-grade glioma who had a sustained objective partial response for 15 cycles, with long-term tolerability and a progression-free survival of 12.9 months.

As noted, this trial was terminated early due to poor accrual, which Dr Nelson et al stated, “highlight[s] the challenges of clinical trial completion for rare pediatric cancers, especially where increased availability of tumor molecular sequencing and multiple commercially available BRAF inhibitors allow providers to treat patients outside of clinical trials.”

Study authors also noted that combination regimens, such as with MEK and BRAF inhibitors, have since been made available with new studies.

While vemurafenib did appear to be tolerable and offer a potential treatment option for pediatric patients with tumors harboring BRAF mutations, study authors noted, “further conclusions could not be established.”

Source:

Nelson MV, Kim A, Williams PM, et al. Phase II study of vemurafenib in children and young adults with tumors harboring BRAF V600 mutations: NCI-COG pediatric MATCH trial (APEC1621) Arm G. Oncologist. 2024;29(8):732-e1093. doi:10.1093/oncolo/oyae119