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Effect of FGFR2 Alterations on Overall and Progression-Free Survival in Patients Receiving Systemic Therapy for
Ghassan K Abou-Alfa1,2, Kristen Bibeau3, Nikolaus Schultz4
1Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA. abou-alg@mskcc.org.
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.
