Real-World Evidence of Natural History of Advanced CCA with FGFR2 Gene Fusion/Rearrangement or Wild-Type FGFR2

Real-world evidence demonstrates a survival advantage for patients with CCA harboring FGFR2 fusions/rearrangements compared with those with FGFR2 wild-type CCA.

A retrospective, observational study was conducted to assess the natural history of patients with advanced cholangiocarcinoma (CCA) and FGFR2 fusions/rearrangements compared with those with wild-type (WT) FGFR2. Results of this real-world analysis were presented at the 2021 American Society of Clinical Oncology Annual Meeting.

This study used a US-based, nationwide deidentified Flatiron Health-Foundation Medicine CCA clinicogenomic database that included data from 280 US cancer clinics to compare the 2 groups of patients with CCA. Inclusion criteria were age ≥18 years, confirmed diagnosis of advanced CCA, comprehensive genomic profiling, and ≥2 visits within the Flatiron Health network since January 1, 2011. The primary study objective was to assess overall survival (OS) in patients with FGFR2 fusions/rearrangements and WT FGFR2 from date of diagnosis to date of death from any cause. The key secondary objective was to evaluate the impact of FGFR status on OS after adjusting for potential prognostic variables.

At the date of analysis—May 2020—a total of 571 eligible patients were included in the study. Of these, 75 patients harbored FGFR2 fusions/rearrangements and 496 patients had WT FGFR2. In the FGFR2 fusions/rearrangements cohort, the median age was 63 years, 64% of the patients were female, 95% had intrahepatic CCA (iCCA), and 68% had stage IV disease at diagnosis. In the WT FGFR2 cohort, the median age was 65 years, 48% of the patients were female, 74% had iCCA, and 55% had stage IV disease at diagnosis.

OS analysis (from the time of advanced CCA) demonstrated that median OS was numerically higher in the FGFR2 fusions/rearrangements group compared with the FGFR2 WT group, which did not reach statistical significance (12.1 months; 95% confidence interval [CI], 8.5-17.1 vs 7.1 months; 95% CI, 5.7-8.8, respectively; log rank P = .184). Similarly, in the iCCA subgroup of 437 patients, the median OS was numerically higher in the FGFR2 fusions/rearrangements group than in the FGFR2 WT group but did not differ significantly (12.1 months; 95% CI, 8.4-17.1 vs 7.8 months; 95% CI, 6.1-10.0, respectively; log rank P = .375). In univariate, bivariate, or multivariate models (after adjusting for potential prognostic covariates), FGFR2 status was not found to be a significant factor contributing to OS. Statistically significant prognostic factors included such patient characteristics as Eastern Cooperative Oncology Group performance status, advanced disease category, and gender.

Based on results of this real-world study, the authors concluded that CCA with FGFR2 fusions/rearrangements was not associated with a statistically significant survival advantage compared with FGFR2 WT CCA among patients receiving therapies for advanced disease, although a trend toward longer OS was observed in patients with FGFR2 fusions/rearrangements.

Source: Shroff RT, Rearden J, Li A, et al. Natural history of patients (pts) with advanced cholangiocarcinoma (CCA) with FGFR2 gene fusion/rearrangement or wild-type (WT) FGFR2. J Clin Oncol. 2021;39(suppl_15):4089-4089.