Cross-Comparison of Clinical Trials Assessing Futibatinib and Pemigatinib versus Chemotherapy in Patients with CCA and FGFR2 Fusion or Other Rearrangements

2022 Year in Review: Cholangiocarcinoma — January 4, 2023

The phase 2 FOENIX-CCA2 clinical trial evaluated the investigational FGFR1-4 inhibitor futibatinib in patients with advanced intrahepatic cholangiocarcinoma (iCCA) harboring FGFR2 fusion or other rearrangements.

In the absence of head-to-head clinical trials comparing the currently available FGFR inhibitors, an indirect treatment comparison was conducted of efficacy outcomes that have been previously published with futibatinib therapy from the FOENIX-CCA2 study versus outcomes with chemotherapy plus FGFR inhibitors. These results were presented at the 2022 ASCO GI Cancers Symposium.

This systematic literature review identified clinical trials with FGFR inhibitors that were published between January 2015 and February 2021 and used additional targeted searches for chemotherapy data. Borad and colleagues used the population-adjusted simulated treatment comparison method and applied individual-level patient data from FOENIX-CCA2 as well as published aggregate data from comparator clinical trials, adjusting for between-study differences in baseline characteristics.

Population-adjusted Cox regression models were used for base-case time-to-event outcomes, including progression-free survival (PFS), overall survival (OS), duration of response (DOR), and binomial-logistic regressions for binary outcomes, namely, objective response rate (ORR).

Two studies were identified for FGFR inhibitors in previously treated patients with FGFR2 fusion or other rearrangements—FOENIX-CCA2 for futibatinib (N = 103) and FIGHT-202 for pemigatinib (N = 107). For chemotherapy in this setting, 2 studies were identified—an analysis of previous systemic therapy in the FIGHT-202 cohort (N = 53), and a natural history study using a clinicogenomic database (N = 71).

In the base-case analysis of futibatinib versus chemotherapy, the patients who received futibatinib had a significantly longer PFS (hazard ratio [HR], 0.53) and OS (HR, 0.49) compared with chemotherapy. In the base-case comparisons of futibatinib versus pemigatinib, treatment with futibatinib was associated with a numerical advantage for all the efficacy parameters, including PFS (HR, 0.89), OS (HR, 0.83), DOR (HR, 0.75), and ORR (HR, 1.43); however, these outcomes did not reach statistical significance.

These data show that futibatinib provides a survival advantage compared with chemotherapy in previously treated patients with advanced iCCA harboring FGFR2 fusion or other rearrangements. In addition, although significant differences in efficacy outcomes were not found between futibatinib and pemigatinib, the numerical trends favored futibatinib over pemigatinib in patients with iCCA, the researchers noted.

Source: Borad MJ, Paine A, Wacheck V, et al. Indirect treatment comparison of futibatinib with chemotherapy and pemigatinib in cholangiocarcinoma with FGFR2 fusions/rearrangements. American Society of Clinical Oncology Gastrointestinal Cancers Symposium 2022. Abstract 440.

Related Items

First-Line Treatment of Advanced Biliary Tract Cancers (BTCs)
Ask the Expert
Use of first-line (1L) IMFINZI® (durvalumab) in combination with gemcitabine and cisplatin (gem-cis) chemotherapy in patients with locally advanced or metastatic biliary tract cancers
KEYNOTE-966: Pembrolizumab Combined With GemCis Versus GemCis Alone in Patients With BTC
2023 Year in Review: Cholangiocarcinoma
In the KEYNOTE-966 study, pembrolizumab was added to gemcitabine/cisplatin to assess outcomes in patients with advanced biliary tract cancer.
Post-hoc Analysis of the ABC-01, -02, and -03 Trials in Patients With Advanced eCCA
2023 Year in Review: Cholangiocarcinoma
This post-hoc analysis of the ABC-01, -02, and -03 clinical trials provides reference survival data for patients with advanced extrahepatic cholangiocarcinoma treated with first-line gemcitabine/cisplatin chemotherapy.
Efficacy and Safety of Tinengotinib in Patients With Advanced Refractory/Relapsed CCA Who Previously Received an FGFR Inhibitor
2023 Year in Review: Cholangiocarcinoma
Investigators pooled data from 3 trials to evaluate tinengotinib in patients with advanced, refractory/relapsed cholangiocarcinoma who previously received an FGFR inhibitor.
KLF5 Inhibition Reduces Tumor Growth and Sensitizes to Chemotherapy-Induced Cell Death in Experimental Models of CCA
2023 Year in Review: Cholangiocarcinoma
Researchers evaluated KLF5 expression and its inhibition in cholangiocarcinoma using clustered regularly interspaced short palindromic repeats technology.
Phase 2 Trial of SHR-1316 Plus IBI310 in Patients With Advanced iCCA After Inadequate Response to First-Line Therapy
2023 Year in Review: Cholangiocarcinoma
In this ongoing phase 2 study, the efficacy of SHR-1316 plus IBI310 is being evaluated in patients with advanced intrahepatic cholangiocarcinoma after inadequate response to first-line therapy.
Examination of Patients With CCA Treated With Novel Targeted Therapies After Extended Molecular Profiling on Liquid Biopsies
2023 Year in Review: Cholangiocarcinoma
Dr Mahmood presented results from the largest multi-institutional review of efficacy outcomes following targeted agents in patients with cholangiocarcinoma.
Phase 2 Component of the BEER-BTC Study: Comparing Bevacizumab Plus Erlotinib Maintenance Versus Observation in Patients With Advanced BTC
2023 Year in Review: Cholangiocarcinoma
In the phase 2 component of the phase 2/3 BEER-BTC study, bevacizumab plus erlotinib improved outcomes in patients with advanced biliary tract cancers.
The DEBATE Trial: Neoadjuvant Durvalumab Plus GemCis Versus GemCis Alone for Patients With Localized BTC
2023 Year in Review: Cholangiocarcinoma
Researchers investigated the efficacy and safety of neoadjuvant durvalumab plus gemcitabine/cisplatin (GemCis) versus GemCis alone in patients with biliary tract cancer.
The Phase 2 ADJUBIL Study of Durvalumab Plus Tremelimumab With or Without Capecitabine in BTC
2023 Year in Review: Cholangiocarcinoma
In the ongoing phase 2 ADJUBIL study, the clinical activity of immunotherapies durvalumab and tremelimumab with or without capecitabine is being assessed in patients with resectable biliary tract cancer in the adjuvant setting.

Subscribe Today!

To sign up for our newsletter or print publications, please enter your contact information below.

I'd like to receive: