Results of the retrospective analysis of phase 2 study of the FGFR1-3 selective tyrosine kinase inhibitor infigratinib indicate that efficacy outcomes in patients with CCA and FGFR2 fusions were better with third- or later-line infigratinib therapy compared with standard second-line chemotherapy.
The most common biliary tract malignancy is CCA, with an estimated annual incidence of 8000 to 10,000 in US patients. The most common second-line treatment is chemotherapy. Response rates are <10%, and median progression-free survival (PFS) is 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. Multiple targeted agents are in development for patients with FGFR2 fusions. Currently, the outcome is unknown in patients with CCA and FGFR2 fusions who receive standard second-line chemotherapy.
After receiving treatment with gemcitabine-based chemotherapy, patients with advanced CCA and FGFR2 fusions or translocations 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. Cycles were 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 treatment with infigratinib) 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 this year’s annual meeting of the American Society of Clinical Oncology (ASCO).
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. Median PFS with standard second-line chemotherapy was 4.63 months compared with 6.8 months for third- or later-line therapy with infigratinib. For second-line chemotherapy, the best overall response rate (ORR) 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, median PFS and ORRs were better with third- or later-line therapy with infigratinib versus standard second-line chemotherapy.
Source: Javle MM, et al. J Clin Oncol. 2020;38(15_suppl). Abstract 4591.
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