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Title: Effect of FGFR2 Alterations on Overall and Progression-Free Survival in Patients Receiving Systemic Therapy for Intrahepatic Cholangiocarcinoma.
Author: Abou-Alfa GK, Bibeau K, Schultz N, Yaqubie A, Millang B, Ren H, Féliz L.
Journal: Target Oncol; 2022 Sep; 17(5):517-527. PubMed ID: 36114955.
Abstract:
BACKGROUND: First-line standard-of-care therapy for advanced cholangiocarcinoma is gemcitabine plus cisplatin; there is no established second-line systemic therapy. Fibroblast growth factor receptor (FGFR)-2 fusions/rearrangements can be oncogenic drivers, occurring almost exclusively in intrahepatic cholangiocarcinoma, but little is known about whether FGFR2 status affects the response to systemic chemotherapy. OBJECTIVE: We aimed to evaluate the effects of FGFR2 status on survival outcomes in patients receiving systemic therapy for intrahepatic cholangiocarcinoma. METHODS: In this retrospective analysis, patients treated with systemic therapy at Memorial Sloan Kettering Cancer Center for intrahepatic cholangiocarcinoma were categorized into three cohorts: FGFR2 fusions; other FGFR2 alterations; no FGFR2 alterations. Endpoints were overall survival and progression-free survival per therapy line. RESULTS: In total, 132 patients with intrahepatic cholangiocarcinoma were included (FGFR2 fusions, n = 15; other FGFR2 alterations, n = 2 [data not reported]; no FGFR2 alterations, n = 115). First-line therapy was platinum based in 93% of patients; 80% received platinum/pyrimidine-based second-line therapy. For patients with FGFR2 fusions and no FGFR2 alterations, respectively, median overall survival from diagnosis was 31.3 months (95% confidence interval [CI] 5.8-not estimable months) [n = 9] and 21.7 months (95% CI 16.1-26.6) [n = 109]; median progression-free survival in first-line therapy was 6.2 months (95% CI 2.0-16.8) [n = 15] and 7.2 months (95% CI 5.0-8.3) [n = 107], and median progression-free survival in second-line therapy was 5.6 months (95% CI 2.8-10.3) [n = 8] and 3.7 months (95% CI 2.6-5.6) [n = 81]. CONCLUSIONS: Patients with intrahepatic cholangiocarcinoma and FGFR2 fusions may have a better prognosis than those without FGFR2 alterations in terms of overall survival, and progression-free survival on second-line, but not first-line systemic therapy. Progression-free survival improvement on second-line chemotherapy may imply an important impact of prior chemotherapy as first line. Intrahepatic cholangiocarcinoma (iCCA) can be caused by changes in many different genes. One type of change in iCCA is a fibroblast growth factor receptor 2 gene (FGFR2) fusion. In fusions, the FGFR2 gene has fused to another gene. Our study examined people with iCCA to compare the overall survival following diagnosis for people with FGFR2 changes and people without. We also measured progression-free survival, which is the time from their first chemotherapy dose until their cancer got worse. All participants had iCCA and their first or second treatment was chemotherapy. Fifteen participants had FGFR2 fusions and 115 had no FGFR2 changes. We found that participants with FGFR2 fusions lived longer (median 31 months) than those without these fusions (median 22 months). During their first treatment, median progression-free survival was similar for participants with and without FGFR2 fusions. After the second chemotherapy, median progression-free survival was about 2 months longer for participants with FGFR2 fusions than those without. Results will vary from person to person and will depend on other factors. However, people with iCCA with FGFR2 fusions may stay slightly longer on their second treatment without their cancer getting worse. With chemotherapy, they may also live somewhat longer than those without FGFR2 fusions.

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