TY - JOUR
T1 - RAF inhibitor re-challenge therapy in BRAF-aberrant pan-cancers
T2 - the RE-RAFFLE study
AU - Nelson, Blessie Elizabeth
AU - Roszik, Jason
AU - Ahmed, Jibran
AU - Barretto, Carmelia Maria Noia
AU - Nardo, Mirella
AU - Campbell, Erick
AU - Johnson, Amber M.
AU - Piha-Paul, Sarina A.
AU - Oliva, Isabella C.Glitza
AU - Weathers, Shiao Pei
AU - Cabanillas, Maria
AU - Javle, Milind
AU - Meric-Bernstam, Funda
AU - Subbiah, Vivek
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/12
Y1 - 2024/12
N2 - 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.
AB - 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.
KW - BRAF inhibitors
KW - BRAF-altered solid tumors
KW - RAF pathway
KW - Rechallenge
UR - http://www.scopus.com/inward/record.url?scp=85188655810&partnerID=8YFLogxK
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U2 - 10.1186/s12943-024-01982-4
DO - 10.1186/s12943-024-01982-4
M3 - Letter
C2 - 38532456
AN - SCOPUS:85188655810
SN - 1476-4598
VL - 23
JO - Molecular cancer
JF - Molecular cancer
IS - 1
M1 - 64
ER -