Real-world data are limited regarding the natural history of patients with advanced cholangiocarcinoma (CCA) and FGFR2 fusion or other rearrangements who are receiving therapies for advanced disease. Rachna T. Shroff, MD, of the University of Arizona Cancer Center, Tucson, and colleagues conducted a retrospective, observational natural history study to compare real-world overall survival (OS) in patients with advanced CCA and FGFR2 fusion or other rearrangements versus patients with wild-type FGFR2 from the diagnosis of advanced CCA to death. Dr Shroff presented the study results at the 2022 ASCO GI Cancers Symposium.
The study’s secondary objective was the OS in a subgroup of patients with CCA and FGFR2 fusion or other rearrangements from the start of the second-line therapy to death.
Dr Shroff and colleagues collected these longitudinal clinical data on patients with CCA from the Flatiron Health-Foundation Medicine clinico-genomic database that includes data from 280 cancer clinics in the United States.
Study inclusion criteria included age ≥18 years, diagnosis of advanced CCA (defined as stage III or IV, or unknown stage and confirmed locoregional or distance recurrence or progression event); comprehensive genomic profiling; and ≥2 visits within the Flatiron Health network since January 1, 2011.
The full analysis set included 571 eligible patients diagnosed with CCA between January 1, 2011, and May 1, 2020. Of these, 75 patients harbored FGFR2 fusion or other rearrangements, and 496 patients had CCA and wild-type FGFR2, including 74% of the patients with intrahepatic CCA.
In the cohort of 75 patients with FGFR2 fusion or rearrangements, the median age was 63 years, 64% were female, 95% had intrahepatic CCA, and 68% had stage IV disease at diagnosis. Among the 496 patients with wild-type FGFR2, the median age was 65 years, 48% were female, 74% had intrahepatic CCA, and 55% had stage IV disease at diagnosis. In the cohort with FGFR2 fusion or rearrangements, 50 patients (94%, intrahepatic CCA; 70%, stage IV disease at diagnosis) received second-line therapy.
Based on Kaplan-Meier plots of real-world OS from the time of advanced CCA, the median OS was numerically higher in the FGFR2 fusion or rearrangements group compared with those with wild-type FGFR2, but the difference was not significant: 12.1 months (95% confidence interval [CI], 8.5-17.1) versus 7.1 months (95% CI, 5.7-8.8; log rank P = .184), respectively. By stratified multivariate analysis, having FGFR2 status was not a significant factor for OS. By contrast, statistically significant prognostic factors were patient characteristics, including ECOG performance status, advanced disease, and gender.
Similarly, in the intrahepatic CCA subgroup of 437 patients, the median OS was numerically higher in the FGFR2 fusion or rearrangements group, but this was not statistically different—12.1 months (95% CI, 8.4-17.1) versus 7.8 months (95% CI, 6.1-10.0; log rank P = .375). In the subgroup of 50 patients with FGFR2 fusion or rearrangements who received second-line therapy, the median real-world OS from the index date of second-line therapy was 8.5 months (95% CI, 4.1-12.4 months).
These results showed no statistically significant survival advantage in patients with FGFR2 fusion or other rearrangements compared with FGFR2 wild-type CCA who received therapies for advanced disease, although a nonsignificant trend toward longer OS was observed in patients with FGFR2 fusion or other rearrangements.
Shroff RT, Avogadri F, Weng R, et al. Natural history of patients with advanced cholangiocarcinoma and FGFR2 gene fusions/rearrangements. Abstract 391.
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