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 (FGFR) 2 fusions occur in 13% to 17% of patients with CCA, and multiple targeted agents are in development for patients with FGFR2 fusions. To date, the outcome of patients with CCA and FGFR2 fusions who receive standard second-line chemotherapy is unknown.
Patients with advanced CCA and FGFR2 fusions or translocations after receiving treatment with gemcitabine-based chemotherapy were enrolled in a single-arm phase 2 study and received the FGFR1-3 selective tyrosine kinase inhibitor infigratinib 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
In a retrospective analysis of a subset of patients who received infigratinib as third-line or later treatment, investigators calculated the PFS (assessed by investigator) and best overall response (per Response Evaluation Criteria in Solid Tumors, version 1.1) after second-line chemotherapy (before infigratinib treatment) and third-line or later treatment with infigratinib.
The study was led by Milind M. Javle, MD, Professor, Department of Gastrointestinal Medical Oncology, M.D. Anderson Cancer Center, Houston, TX, and the results were presented at the 2020 ASCO annual meeting.
A total of 71 patients with FGFR2 fusions were enrolled at the time of analysis, and 37 (52%) patients were included in the retrospective analysis. The median PFS with standard second-line chemotherapy was 4.63 months compared with 6.8 months for third- or later-line therapy with infigratinib.
The best overall response rate (ORR) for second-line chemotherapy was 5.4% compared with 21.6% for third- or later-line therapy with infigratinib. The investigators concluded that in patients with CCA and FGFR2 fusions, the median PFS and ORRs were better with third- or later-line therapy with infigratinib than with standard second-line chemotherapy.
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