FGFR2 rearrangement

In the first-line setting, gemcitabine plus cisplatin (GemCis) chemotherapy served as the long-standing standard of care; subsequently, TOPAZ-1 and KEYNOTE-966 established GemCis plus durvalumab or pembrolizumab as the current standard. For patients who progressed after frontline therapy and lack actionable alterations, fluoropyrimidine plus oxaliplatin and fluoropyrimidine plus liposomal irinotecan are recommended second-line options, supported by ABC-06 and NIFTY, respectively...Although recent advances have improved clinical outcomes in patients with advanced BTC, median overall survival remains around 1 year, underscoring the need for further therapeutic innovation. This review provides a comprehensive overview of the current standards of care and highlights emerging therapeutic strategies for advanced BTC.

Our findings provided preliminary evidence that novel FGFR2 fusions might act as primary oncogenic drivers in a rare subset of KIT/PDGFRA wild-type GISTs. These cases highlight the importance for comprehensive genomic profiling and suggest that fibroblast growth factor receptor-targeted inhibitors could be a potential therapeutic strategy for advanced or imatinib-resistant diseases, warranting further investigation in larger cohorts.

P2, N=83, Terminated, Incyte Corporation | Completed --> Terminated; Recruitment ceased after a pre-planned futility interim analysis indicated a low probability to confer a clinically meaningful improvement in objective response when compared to currently available therapies. There were no safety related concerns.

The FGFR2 positivity rate in Asia is slightly lower but consistent with Japanese reports and is more common in younger patients with ICC. Distinct genetic alterations may characterize Asian populations.

P1, N=169, Active, not recruiting, Abbisko Therapeutics Co, Ltd | Recruiting --> Active, not recruiting

P3, N=167, Terminated, Incyte Corporation | Trial completion date: Jul 2028 --> Jul 2025 | Active, not recruiting --> Terminated | Trial primary completion date: Oct 2027 --> Jul 2025; The study was terminated due to lack of enrollment resulting from a change in the standard of care for the first-line treatment of patients with cholangiocarcinoma. There were no safety concerns that contributed to this decision.

Here, we report a case of FGFR2-rearranged iCCA where the patient achieved a radiographic partial response (PR) to tasurgratinib (a third-line FGFR inhibitor) following prior progression on pemigatinib and futibatinib. More broadly, this report serves as a basis for a current opinion on the evolving landscape of sequential FGFR inhibition in iCCA. We delve into the complexities of acquired resistance, dissect the arguments for and against prolonged FGFR pathway blockade, explore the impact of co-occurring genomic alterations, discuss the controversies, research priorities, and the urgent need for a balanced perspective to guide future clinical practice and trial design in this rapidly advancing but still uncertain field.

Objective response rates, disease control rates, and a PFS comparable to that in the phase 2 FIGHT-202 trial was reported with pemigatinib use in this Canadian PSP cohort.

P1, N=169, Recruiting, Abbisko Therapeutics Co, Ltd | Trial completion date: Jun 2025 --> Jun 2026 | Trial primary completion date: Mar 2025 --> Mar 2026

Therefore, it is necessary to understand the clinicopathological features and prognostic factors of iCCA, pCCA and distal cholangiocarcinoma (dCCA). In addition, lymph node status is likely to be an independent and important prognostic factor.