Abstract 304P
Background
Different FGFR2-targeting agents have been approved for patients with FGFR2 rearranged intrahepatic cholangiocarcinoma (iCCA), including non-covalent ones or covalent irreversible inhibitors such as futibatinib. Preclinically, futibatinib has proved active against models with acquired FGFR2 mutations of resistance to non-covalent inhibitors. However, limited evidence has been presented to date for the efficacy of futibatinib in patients progressing under treatment with a non-covalent inhibitor.
Methods
Between January 2021 and April 2023, 14 patients received futibatinib after treatment with the non-covalent FGFR inhibitors pemigatinib (10 patients) or derazantinib (4 patients). Foundation Medicine One CDx (7 patients) or Liquid (2 patients) next-generation DNA sequencing (NGS) was used on samples collected at progression to demonstrate evidence of acquired FGFR2 mutations. Patients received oral futibatinib at a dose of 20 mg daily in a continuous regimen as part of the compassionate use program of Taiho Oncology.
Results
The median progression free survival (mPFS) and the objective response rate with previous non-covalent inhibitors were 10.7 months (IQR, 6.8-14.2) and 54.5%, respectively. The most frequent acquired resistance mutation was FGFR2 N549x (77.8%). Using futibatinib, four patients (28.6%) obtained a radiological partial response, and three (21.4%) had stable disease, accounting for a disease control rate of 50.0%. With a median follow-up of 25.4 months (IQR, 15-33), mPFS and overall survival were 4.5 months (IQR, 3.4-8.8) and 9.8 months (IQR, 6-23), respectively. The most common treatment-related adverse events of any grade were hyperphosphatemia (71.4%) and palmar-plantar erythrodysesthesia syndrome (35.7%).
Conclusions
Futibatinib was manageable and active in patients with iCCA progressing under a previously non-covalent FGFR2 inhibitor. Randomized controlled trials are needed to determine the optimal therapeutic approach between an upfront treatment with a covalent inhibitor or a sequential strategy starting with a non-covalent inhibitor, followed by a covalent one if disease progresses due to acquired mutations that this could address.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
A. Vogel: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Boehringer Mannheim, Eisai, Incyte, Ipsen, Janssen, MSD, Pierre Fabre, Roche, Servier, Tyra, Tahio; Financial Interests, Personal, Invited Speaker: BMS, Eisai, Ipsen, Lilly, MSD, Roche, AstraZeneca, Roche, MSD, BeiGene, Jiangsu Hengrui Medicines. D. Melisi: Financial Interests, Personal, Advisory Board: Incyte co., Servier, iOnctura, Tahio; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Research Grant: iOnctura. All other authors have declared no conflicts of interest.