Effect of FGFR2 alterations on overall and progression-free survival in patients receiving systemic therapy for intrahepatic cholangiocarcinoma Journal Article
| Authors: | Abou-Alfa, G. K.; Bibeau, K.; Schultz, N.; Yaqubie, A.; Millang, B.; Ren, H.; Féliz, L. |
| Article Title: | Effect of FGFR2 alterations on overall and progression-free survival in patients receiving systemic therapy for intrahepatic cholangiocarcinoma |
| 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. © 2022, Incyte Corporation. |
| Keywords: | adult; controlled study; retrospective studies; major clinical study; overall survival; genetics; mutation; cisplatin; fluorouracil; cancer combination chemotherapy; drug efficacy; drug safety; monotherapy; systemic therapy; treatment duration; gemcitabine; progression free survival; cohort analysis; gene function; pathology; pyrimidines; retrospective study; irinotecan; confidence interval; oncogene; cancer center; health status; folinic acid; gene fusion; intrahepatic cholangiocarcinoma; bile duct carcinoma; bile duct neoplasms; bile ducts, intrahepatic; cholangiocarcinoma; platinum derivative; oxaliplatin; pyrimidine derivative; fibroblast growth factor receptor 2; receptor, fibroblast growth factor, type 2; pyrimidine; bile duct cancer; progression-free survival; intrahepatic bile duct; cancer prognosis; humans; human; male; female; article; fgfr2 protein, human; infigratinib; fgfr2 gene; isocitrate dehydrogenase inhibitor; pemigatinib; futibatinib |
| Journal Title: | Targeted Oncology |
| Volume: | 17 |
| Issue: | 5 |
| ISSN: | 1776-2596 |
| Publisher: | Springer |
| Date Published: | 2022-09-01 |
| Start Page: | 517 |
| End Page: | 527 |
| Language: | English |
| DOI: | 10.1007/s11523-022-00906-w |
| PUBMED: | 36114955 |
| PROVIDER: | scopus |
| PMCID: | PMC9512879 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 November 2022 -- Source: Scopus |
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