Dr Milind Javle of the the University of Texas MD Anderson Cancer Center in Houston, TX, US and colleagues reported at ESMO World Congress on Gastrointestinal Cancer 2020 Virtual (1-4 July) that outcomes from second-line chemotherapy in patients with cholangiocarcinoma and fibroblast growth factor receptor 2 (FGFR2) fusions are similar to those reported in the literature for all patients with cholangiocarcinoma regardless of genomic status and remain dismal. Selective FGFR1-3 inhibitor, infigratinib administered as third- and later-line treatment resulted in a meaningful progression-free survival (PFS) and overall response rate (ORR) benefit in patients with cholangiocarcinoma and FGFR2 fusions.
The study team reported that cholangiocarcinoma is the most common biliary tract cancer with an estimated incidence of 1.67/100,000 in the US and 0.45‒3.36/100,000 in Europe.
Chemotherapy is the most common second-line treatment in patients with cholangiocarcinoma.
FGFR2 fusions occur in 13-17% of cholangiocarcinoma and several targeted tyrosine kinase inhibitors are in development for this patient population. However, the outcome of patients with cholangiocarcinoma and FGFR2 fusions receiving standard second-line chemotherapy is unknown.
Patients with advanced cholangiocarcinoma and FGFR2 fusions after prior treatment with gemcitabine-based chemotherapy were enrolled in a single-arm phase II study (NCT02150967) and received infigratinib (previously know as BGJ398) 125 mg orally once daily on days 1-21. Cycles were repeated every 28 days until unacceptable toxicity, disease progression, investigator discretion, or withdrawal of consent.
A retrospective analysis of a subset of patients who received infigratinib as third- or later-line treatment was performed. Investigator-assessed PFS and ORR per RECIST v1.1 following second-line chemotherapy (pre-infigratinib) and third-line or later-line therapy with infigratinib were calculated.
Of the 71 patients, 44 were women; a median age was 53 years. Of these patients with FGFR2 fusions who were enrolled at the time of analysis (data cut, 8 August 2018), 37 patients (52%) were included in this retrospective analysis.
Median PFS with standard second-line chemotherapy was 4.63 months (95% confidence interval [CI] 2.69-7.16) compared with 6.77 months (95% CI 3.94-7.79) for third- and later-line infigratinib.
The ORR for second-line chemotherapy was 5.4% (95% CI 0.7-18.2) compared with 21.6% (95% CI 9.8-38.2) for third- and later-line infigratinib.
The authors concluded that outcomes from second-line chemotherapy in patients with cholangiocarcinoma and FGFR2 fusions were similar to those reported in the literature for all patients with cholangiocarcinoma regardless of genomic status and remain dismal. Infigratinib administered as third- and later-line treatment resulted in a meaningful benefit.
This study was funded by QED Therapeutics Inc.
Abstract SO-5. Javle M, Sadeghi S, Roychowdhury S, et al. Efficacy of second-line chemotherapy in patients with advanced or metastatic cholangiocarcinoma and FGFR2 fusions: A retrospective analysis. ESMO World Congress on Gastrointestinal Cancer 2020 Virtual (1-4 July).