RAF Inhibitor Re-Challenge Therapy in BRAF-Aberrant Pan-Cancers: The Re-Raffle Study

Authors

Blessie Elizabeth Nelson
Jason Roszik
Jibran Ahmed
Carmelia Maria Noia Barretto
Mirella Nardo
Erick Campbell
Amber M Johnson
Sarina A Piha-Paul
Isabella C Glitza Oliva
Shiao-Pei Weathers
Maria Cabanillas
Milind Javle
Funda Meric-Bernstam
Vivek Subbiah

Publication Date

3-26-2024

Journal

Molecular Cancer

Abstract

Previous studies have shown the clinical benefit of rechallenging the RAF pathway in melanoma patients previously treated with BRAF inhibitors. 44 patients with multiple tumors harboring RAF alterations were rechallenged with a second RAF inhibitor, either as monotherapy or in combination with other therapies, after prior therapy with a first RAF inhibitor. This retrospective observational study results showed that rechallenging with RAFi(s) led to an overall response rate of 18.1% [PR in thyroid (1 anaplastic; 3 papillary), 1 ovarian, 2 melanoma, 1 cholangiocarcinoma, and 1 anaplastic astrocytoma]. The clinical benefit rate was 54.5%; more than 30% of patients had durable responses with PR and SD lasting > 6 months. The median progression-free survival on therapy with second RAF inhibitor in the rechallenge setting either as monotherapy or combination was shorter at 2.7 months (0.9-30.1 m) compared to 8.6 months (6.5-11.5 m) with RAF-1i. However, the median PFS with RAF-2i responders (PFS-2) improved at 12.8 months compared to 11.4 months with RAF-1i responders. The median OS from retreatment with RAF-2i was 15.5 months (11.1-30.8 m). Further prospective studies are needed to validate these results and expand targeted therapy options for RAF-aberrant cancers.

Keywords

Humans, Melanoma, Proto-Oncogene Proteins B-raf, Protein Kinase Inhibitors, Retrospective Studies, Prospective Studies, Mutation

Comments

Supplementary Materials

Data Availability Statement

PMID: 38532456