Efficacy of second-line chemotherapy in patients with advanced or metastatic cholangiocarcinoma and FGFR2 fusions: A retrospective analysis

Cholangiocarcinoma (CCA) is the most common biliary tract malignancy 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 with reported outcomes in patients with CCA. Response rates of J Clin Oncol 2019, abstract 4003]. Fibroblast growth factor receptor 2 (FGFR2) fusions occur in 13–17% of CCA and several targeted tyrosine kinase inhibitors (TKI) are in development for patients with CCA and 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 after prior treatment with gemcitabine-based chemotherapy were enrolled in a single-arm phase 2 study (NCT02150967) and received the FGFR1–3 selective TKI infigratinib (previously BGJ398) 125 mg orally once daily on days 1–21, cycles 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 objective response rate (ORR, per RECIST 1.1) following second-line chemotherapy (pre-infigratinib) and third-line or later-line therapy with infigratinib were calculated. Of the 71 patients (44 women; median age 53 years) with FGFR2 fusions enrolled at the time of analysis (datacut, 8 August 2018), 37 (52%) were included in this retrospective analysis. Median PFS with standard second-line chemotherapy was 4.63 months (95% CI 2.69–7.16) compared with 6.77 months (95% CI 3.94–7.79) for third- and later-line infigratinib. 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. Outcomes from second-line chemotherapy in patients with CCA and FGFR2 fusions were similar to those reported in the literature for all patients with CCA regardless of genomic status and remain dismal. Infigratinib administered as third- and later-line treatment resulted in a meaningful PFS and ORR benefit in patients with CCA and FGFR2 fusions.