BRAF-targeted therapy for locally advanced ameloblastoma of the mandible: A potential neoadjuvant strategy.

Abstract

3149 Background: Ameloblastoma is a rare benign but locally aggressive odontogenic neoplasm, with 2% of cases representing ameloblastic carcinoma or metastatic ameloblastoma. It affects young adults with high recurrence rates after surgery. The standard therapy is radical bone resection with subsequent functional, aesthetic & psychological impairments. Therefore, other therapeutic options, including neoadjuvant approach, should be considered. Sixty to 70% of mandible Ameloblastoma carry a BRAF mutation, usually V600E, and previous case reports have shown durable responses to treatment with BRAF inhibitors in these patients. We sought to explore the possibility of neoadjuvant BRAF or BRAF+MEK inhibition as neoadjuvant treatment in mandible Ameloblastoma. Here we present results of 12 patients with locally advanced disease who were treated with BRAF with or without MEK inhibitors. Methods: Patients who were unable to undergo jaw preservation surgery for locally advanced Ameloblastoma with a BRAF V600E mutation were treated with Dabrafenib or Dabrafenib-Tratmetinib in an EAP form. Patient records were analyzed for baseline parameters, treatment regimen, toxicity, response to therapy and the ability to convert to a mandible preservation surgery. Data were collected and analyzed in accordance with Sheba Medical Center IRB approval. Statistical analyses were done with STATA v.17. Results: Twelve patients were treated with Dabrafenib/ Dabrafenib-Tratmetinib between 2017-2021. Five patients received BRAF-MEK inhibitors and 7 BRAF inhibitor alone. Median age was 21. Ten patients(83%) showed excellent response to therapy and have successfully converted from planned radical bone resection to mandible preservation surgery. The other 2 patients are still on therapy and have also showed deep responses that enable conversion to mandible preservation. Median time to surgery was 10 months. With median follow up of 18 months, no cases of recurrence were documented. Rate of adverse events was as expected with only 1 case of G3-4 (hepatitis). Conclusions: Targeted therapy with BRAF with or without MEK inhibition may serve as an important therapeutic tool for locally advanced Ameloblastoma with the potential of organ preservation treatment, and is an important example of oncological therapy assisting in non-cancerous tumors.