Cholangiocarcinoma (CCA) is the most common biliary tract malignancy, with an estimated incidence of 8000 to 10,000 patients annually in the United States. Chemotherapy is the most common second-line treatment with response rates of <10% and median progression-free survival (PFS) of approximately 3 to 4 months, including FOLFOX in the ABC-06 trial.1 Fibroblast growth factor receptor 2 (FGFR2) fusions occur in 13% to 17% of CCA, and multiple targeted agents are in development for patients with FGFR2 fusions. To date, the outcome of patients with CCA and FGFR2 fusions receiving standard second-line chemotherapy is unknown.
Patients with advanced CCA and FGFR2 fusions or translocations after prior treatment with gemcitabine-based chemotherapy were enrolled in a single-arm phase 2 study (NCT02150967) and received the FGFR1-3 selective tyrosine kinase inhibitor infigratinib (previously BGJ398) 125 mg orally once daily on days 1 to 21, with cycles repeated every 28 days until unacceptable toxicity, disease progression, investigator discretion, or withdrawal of consent.2 A retrospective analysis of a subset of patients who received infigratinib as third- or later-line treatment was performed. Investigator-assessed PFS and best overall response (per RECIST 1.1) following second-line chemotherapy (pre-infigratinib) and third-line or later-line infigratinib were calculated.
A total of 71 patients with FGFR2 fusions enrolled at the time of analysis, and 37 (52%) patients were included in the retrospective analysis. Median PFS with standard second-line chemotherapy was 4.63 months compared with 6.8 months for third- and later-line infigratinib. Best overall response for second-line chemotherapy was 5.4% compared with 21.6% for third- and later-line infigratinib. The authors concluded that in patients with CCA and FGFR2 fusions, median PFS and overall response rate was better for third- and later-line treatment with infigratinib versus standard second-line chemotherapy. ClinicalTrials.gov number NCT02150967.