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.
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.
Authors: Milind Javle; Maeve Lowery; Rachna T Shroff; Karl Heinz Weiss; Christoph Springfeld; Mitesh J Borad; Ramesh K Ramanathan; Lipika Goyal; Saeed Sadeghi; Teresa Macarulla; Anthony El-Khoueiry; Robin Kate Kelley; Ivan Borbath; Su Pin Choo; Do-Youn Oh; Philip A Philip; Li-Tzong Chen; Thanyanan Reungwetwattana; Eric Van Cutsem; Kun-Huei Yeh; Kristen Ciombor; Richard S Finn; Anuradha Patel; Suman Sen; Dale Porter; Randi Isaacs; Andrew X Zhu; Ghassan K Abou-Alfa; Tanios Bekaii-Saab Journal: J Clin Oncol Date: 2017-11-28 Impact factor: 44.544
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Authors: Vincenzo Mazzaferro; Bassel F El-Rayes; Michele Droz Dit Busset; Christian Cotsoglou; William P Harris; Nevena Damjanov; Gianluca Masi; Lorenza Rimassa; Nicola Personeni; Fadi Braiteh; Vittorina Zagonel; Kyriakos P Papadopoulos; Terence Hall; Yunxia Wang; Brian Schwartz; Julia Kazakin; Sherrie Bhoori; Filippo de Braud; Walid L Shaib Journal: Br J Cancer Date: 2018-11-13 Impact factor: 7.640
Authors: Mitesh J Borad; Mia D Champion; Jan B Egan; Winnie S Liang; Rafael Fonseca; Alan H Bryce; Ann E McCullough; Michael T Barrett; Katherine Hunt; Maitray D Patel; Scott W Young; Joseph M Collins; Alvin C Silva; Rachel M Condjella; Matthew Block; Robert R McWilliams; Konstantinos N Lazaridis; Eric W Klee; Keith C Bible; Pamela Harris; Gavin R Oliver; Jaysheel D Bhavsar; Asha A Nair; Sumit Middha; Yan Asmann; Jean-Pierre Kocher; Kimberly Schahl; Benjamin R Kipp; Emily G Barr Fritcher; Angela Baker; Jessica Aldrich; Ahmet Kurdoglu; Tyler Izatt; Alexis Christoforides; Irene Cherni; Sara Nasser; Rebecca Reiman; Lori Phillips; Jackie McDonald; Jonathan Adkins; Stephen D Mastrian; Pamela Placek; Aprill T Watanabe; Janine Lobello; Haiyong Han; Daniel Von Hoff; David W Craig; A Keith Stewart; John D Carpten Journal: PLoS Genet Date: 2014-02-13 Impact factor: 5.917