Effect of FGFR2 alterations on survival in patients receiving systemic chemotherapy for intrahepatic cholangiocarcinoma.
Authors: Abou-Alfa Ghassan K. , Bibeau Kristen , Schultz Nikolaus , Yaqubie Amin , Millang Brittanie M , Ren Haobo , Féliz Luis 
Published: January 2021

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Background: Most patients (pts) with cholangiocarcinoma (CCA) are diagnosed with advanced disease and are ineligible for surgery. FGFR2 fusions/rearrangements are oncogenic drivers and are present almost exclusively in pts with intrahepatic CCA (iCCA; 10–16% of pts); however, little is known about the effects of FGFR2 status on response to systemic chemotherapy. Memorial Sloan Kettering (MSK) obtains genomic sequencing data from almost all iCCA pts treated at the institution. This provides a unique, rich database from which genomic profiling data can be overlaid with clinical data to facilitate a meaningful understanding of pt outcomes, and to suggest potential therapeutic options. This retrospective analysis evaluated progression free survival (PFS) and overall survival (OS) in pts receiving standard systemic chemotherapy (CXT) for iCCA harboring FGFR2 fusions/rearrangements ( FGFR2 +), or harboring wild-type FGFR2 ( FGFR2wt). Methods: Clinical and genomic data were obtained from the MSK database for all iCCA pts to determine disease history and exposure to prior lines (PL) of CXT in the advanced setting. Only pts with complete data for PL of CXT were analyzed. Median PFS and OS were calculated using the Kaplan-Meier method. OS was calculated from diagnosis until death; PFS was calculated from first dose of first line of CXT until progression, death, last visit, relevant dates of later CXT lines; pts with unconfirmed outcomes were censored at last known follow-up date. Results: One-hundred-thirty-two pts were included in this analysis (median age at diagnosis: 62.0 y; 54.5% female; FGFR2+, n = 15; FGFR2wt, n = 115; other FGFR2 alterations, n = 2). Among pts receiving first-line CXT, median PFS was 7.1 months (95% CI: 5.0–8.3) for all pts (n = 124), 6.2 months (2.0–16.8) for FGFR2+ pts (n = 15), and 7.2 months (5.0–8.3) for FGFR2wt pts (n = 107). Among pts with ≥2 PL of CXT (n = 90), median PFS on second-line chemotherapy was 5.6 months (95% CI: 2.8–10.3) for FGFR2+ pts, and 3.7 months (2.6–5.6) for FGFR2wt pts. Median OS was numerically longer in FGFR2+ pts compared with FGFR2wt pts (31.3 months [95% CI: 5.8–not estimable] vs 21.8 months [16.7–26.6]). Conclusions: Among pts receiving standard systemic chemotherapy for iCCA, median PFS was similar in pts harboring FGFR2+ vs FGFR2wt receiving first-line chemotherapy, and relatively longer in pts harboring FGFR2+ receiving second-line chemotherapy. Median OS was longer in FGFR2+ vs FGFR2wt pts. Compared with recently published data in molecularly unselected CCA pts (Lowery. Cancer. 2019; 125: 4426), PFS was similar in pts receiving first-line chemotherapy, and slightly longer for second-line chemotherapy. Data interpretation is limited by the retrospective nature of this analysis of investigator-reported data, the study size, and by the possibility that the analysis population may not reflect the general population of pts with CCA.