Exploring Molecular Genetic Alterations and RAF Fusions in Melanoma: A Belvarafenib Expanded Access Program in Patients with RAS/RAF-Mutant Melanoma

Kyoo Hyun Kim, Sungmin Cho, Yeyeong Jeong, Eun Sil Baek, Chung Lee, Hyang Joo Ryu, Young Su Noh, Yoon Hee Hong, Kee Yang Chung, Mi Ryung Roh, Byung Ho Oh, Chang Gon Kim, Minkyu Jung, Sang Joon Shin

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Melanoma incidence is on the rise in East Asia, yet studies of the molecular landscape are lacking in this population. We examined patients with melanoma who underwent next-generation sequencing (NGS) at a single tertiary center in South Korea, focusing on patients harboring NRAS or RAF alterations who received belvarafenib, a pan-RAF dimer inhibitor, through the Expanded Access Program (EAP). Patients and Methods: Data were collected from 192 patients with melanoma who underwent NGS between November 2017 and May 2023. Variant call format data were obtained and annotated. Patients in the EAP received 450 mg twice daily doses of belvarafenib. Results: Alterations in the RAS/RTK pathway were the most prevalent, with BRAF and NRAS alteration rates of 22.4% and 17.7%, respectively. NGS enabled additional detection of fusion mutations, including 6 BRAF and 1 RAF1 fusion. Sixteen patients with NRAS or RAF alterations received belvarafenib through the EAP, and disease control was observed in 50%, with 2 patients demonstrating remarkable responses. Conclusions: Our study highlights the value of NGS in detecting BRAF, NRAS mutations and RAF fusions, expanding possibilities for targeted therapies in malignant melanoma. Belvarafenib showed clinical benefit in patients harboring these alterations. Ongoing trials will provide further insights into the safety and efficacy of belvarafenib.

Original languageEnglish
Pages (from-to)e811-e821
JournalOncologist
Volume29
Issue number6
DOIs
Publication statusPublished - 2024 Jun

Bibliographical note

Publisher Copyright:
© 2024 The Author(s).

All Science Journal Classification (ASJC) codes

  • General Medicine

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