Milind Javle, MD
At the European Society for Medical Oncology (ESMO) World Congress on Gastrointestinal Cancer 2020 Virtual, Milind Javle, MD, of The University of Texas MD Anderson Cancer Center, Houston, and colleagues reported that third- and later-line treatment with the selective fibroblast growth factor receptor (FGFR) 1–3 inhibitor infigratinib resulted in a progression-free survival and overall response rate benefit for patients with cholangiocarcinoma and FGFR2 fusions.1 The authors also reported that outcomes with 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.”
According to the study team, chemotherapy is the most common second-line treatment in patients with cholangiocarcinoma. FGFR2 fusions occur in 13% to 17% of patients with 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.
Phase II Trial
A total of 71 patients with advanced cholangiocarcinoma and FGFR2 fusions who had undergone prior treatment with gemcitabine-based chemotherapy were enrolled in a single-arm phase II study. Patients received infigratinib (previously known as BGJ398) at 125 mg orally once daily on days 1 to 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 progression-free survival and overall response rate per Response Evaluation Criteria in Solid Tumors, version 1.1, following second-line chemotherapy (before infigratinib) and third-line or later-line therapy with infigratinib were calculated.
Of the 71 patients, 44 were women; the median patient age was 53 years. Of patients with FGFR2 fusions who were enrolled at the time of analysis, 37 patients (52%) were included in this retrospective analysis.
Median progression-free survival with standard second-line chemotherapy was 4.63 months (95% confidence interval [CI] = 2.69–7.16 months) compared with 6.77 months (95% CI = 3.94–7.79) months with third- and later-line infigratinib. The overall response rate 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. According to the authors, infigratinib administered as third- and later-line treatment resulted in a meaningful benefit.
DISCLOSURE: This study was funded by QED Therapeutics, Inc.
1. 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. Abstract SO-5.