TY - JOUR
T1 - FGFR Inhibitor Toxicity and Efficacy in Cholangiocarcinoma
T2 - Multicenter Single-Institution Cohort Experience
AU - Gile, Jennifer J.
AU - Ou, Fang-Shu
AU - Mahipal, Amit
AU - Larson, Joseph J.
AU - Mody, Kabir
AU - Jin, Zhaohui
AU - Hubbard, Joleen
AU - Halfdanarson, Thorvardur
AU - Alberts, Steven R.
AU - Jatoi, Aminah
AU - Mc Williams, Robert R
AU - Ma, Wen Wee
AU - Ilyas, Sumera
AU - Smoot, Rory
AU - Roberts, Lewis Rowland
AU - Gores, Gregory
AU - Borad, Mitesh
AU - Bekaii-Saab, Tanios S.
AU - Tran, Nguyen H.
N1 - Publisher Copyright:
© 2021 by American Society of Clinical Oncology.
PY - 2021
Y1 - 2021
N2 - PURPOSE Cholangiocarcinomas (CCA) are a group of heterogeneous tumors arising from the biliary epithelia. Significant sequencing efforts have provided further insights into the molecular mechanisms of this disease including fibroblast growth factor receptor (FGFR) alterations, which occurs in approximately 15%-20% of intrahepatic CCAs. Herein, we describe the FGFR inhibitor (FGFRi)-associated treatment toxicity and cancer-specific outcomes from a multicenter single-institution cohort. METHODS This is a retrospective study of patients with CCA and known FGFR alterations treated with FGFRi. We describe the toxicity and efficacy in patients treated at Mayo Clinic between January 2010 and December 2020. RESULTS Our group identified 61 patients with advanced or metastatic CCA, 19 males (31%) and 42 females (69%), harboring FGFR alterations who received FGFRi. The most common grade 1 or higher adverse events for all patients included fatigue (92%), AST elevations (78%), anemia (80%), decreased platelet count (63%), and hyperphosphatemia (74%). Median progression-free survival on FGFRi was 5.8 months for all patients (95% CI, 4.9 to 9.0). Females had significantly longer progression-free survival at 6.9 months (95% CI, 5.2 to 11.8) on FGFRi compared with males at 4.9 months (95% CI, 2.8 to not estimable; P = .038). CONCLUSION FGFRi are well tolerated with clinical efficacy. With the recent approval of FGFRi by the US Food and Drug Administration and ongoing clinical trials for new FGFRi, understanding outcomes and toxicity associated with these medications is important for precision oncology.
AB - PURPOSE Cholangiocarcinomas (CCA) are a group of heterogeneous tumors arising from the biliary epithelia. Significant sequencing efforts have provided further insights into the molecular mechanisms of this disease including fibroblast growth factor receptor (FGFR) alterations, which occurs in approximately 15%-20% of intrahepatic CCAs. Herein, we describe the FGFR inhibitor (FGFRi)-associated treatment toxicity and cancer-specific outcomes from a multicenter single-institution cohort. METHODS This is a retrospective study of patients with CCA and known FGFR alterations treated with FGFRi. We describe the toxicity and efficacy in patients treated at Mayo Clinic between January 2010 and December 2020. RESULTS Our group identified 61 patients with advanced or metastatic CCA, 19 males (31%) and 42 females (69%), harboring FGFR alterations who received FGFRi. The most common grade 1 or higher adverse events for all patients included fatigue (92%), AST elevations (78%), anemia (80%), decreased platelet count (63%), and hyperphosphatemia (74%). Median progression-free survival on FGFRi was 5.8 months for all patients (95% CI, 4.9 to 9.0). Females had significantly longer progression-free survival at 6.9 months (95% CI, 5.2 to 11.8) on FGFRi compared with males at 4.9 months (95% CI, 2.8 to not estimable; P = .038). CONCLUSION FGFRi are well tolerated with clinical efficacy. With the recent approval of FGFRi by the US Food and Drug Administration and ongoing clinical trials for new FGFRi, understanding outcomes and toxicity associated with these medications is important for precision oncology.
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U2 - 10.1200/PO.21.00064
DO - 10.1200/PO.21.00064
M3 - Article
C2 - 34778691
AN - SCOPUS:85127548858
SN - 2473-4284
VL - 5
SP - 1228
EP - 1240
JO - JCO Precision Oncology
JF - JCO Precision Oncology
ER -