| Title: |
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 |
| Source: |
Molecular Cancer, Vol 23, Iss 1, Pp 1-11 (2024) |
| Publisher Information: |
BMC, 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| Subject Terms: |
Rechallenge; RAF pathway; BRAF inhibitors; BRAF-altered solid tumors; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; RC254-282 |
| Description: |
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. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1476-4598 |
| Relation: |
https://doaj.org/toc/1476-4598 |
| DOI: |
10.1186/s12943-024-01982-4 |
| Access URL: |
https://doaj.org/article/536748e4fa9d4e778632dfc29b4e5ed7 |
| Accession Number: |
edsdoj.536748e4fa9d4e778632dfc29b4e5ed7 |
| Database: |
Directory of Open Access Journals |