Article
Gastroenterology & Hepatology
Milind Javle, Sameek Roychowdhury, Robin Kate Kelley, Saeed Sadeghi, Teresa Macarulla, Karl Heinz Weiss, Dirk-Thomas Waldschmidt, Lipika Goyal, Ivan Borbath, Anthony El-Khoueiry, Mitesh J. Borad, Wei Peng Yong, Philip A. Philip, Michael Bitzer, Surbpong Tanasanvimon, Ai Li, Amit Pande, Harris S. Soifer, Stacie Peacock Shepherd, Susan Moran, Andrew X. Zhu, Tanios S. Bekaii-Saab, Ghassan K. Abou-Alfa
Summary: Infigratinib has shown promising clinical activity and manageable adverse events in previously treated patients with locally advanced or metastatic cholangiocarcinoma harboring FGFR2 gene fusions or rearrangements, indicating a potential new therapeutic option for this population.
LANCET GASTROENTEROLOGY & HEPATOLOGY
(2021)
Article
Medicine, General & Internal
Lipika Goyal, Funda Meric-Bernstam, Antoine Hollebecque, Juan W. Valle, Chigusa Morizane, Thomas B. Karasic, Thomas A. Abrams, Junji Furuse, Robin K. Kelley, Philippe A. Cassier, Heinz-Josef Kluempen, Heung-Moon Chang, Li-Tzong Chen, Josep Tabernero, Do-Youn Oh, Amit Mahipal, Markus Moehler, Edith P. Mitchell, Yoshito Komatsu, Kunihiro Masuda, Daniel Ahn, Robert S. Epstein, Abdel-Baset Halim, Yao Fu, Tehseen Salimi, Volker Wacheck, Yaohua He, Mei Liu, Karim A. Benhadji, John A. Bridgewater
Summary: In this study, 103 patients with FGFR2-altered intrahepatic cholangiocarcinoma were treated with futibatinib for a median duration of 17.1 months. The results showed that futibatinib treatment could effectively inhibit tumor growth, improve survival, and maintain quality of life for patients.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Review
Pharmacology & Pharmacy
Connie Kang
Summary: Infigratinib, a FGFR-specific tyrosine kinase inhibitor, has been approved in the USA for the treatment of previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with specific genetic abnormalities.
Article
Pharmacology & Pharmacy
Gehan Botrus, Puneet Raman, Thomas Oliver, Tanios Bekaii-Saab
Summary: The FGFR pathway plays a crucial role in cell functions, especially in cancers like IHCA. Infigratinib, as an FGFR inhibitor, has shown promising results in preclinical studies and is being investigated for cancer treatment. Ongoing phase III clinical trials are evaluating its efficacy in treating IHCA with FGFR2 fusions compared to standard treatments.
EXPERT OPINION ON INVESTIGATIONAL DRUGS
(2021)
Article
Oncology
Andrew B. Lassman, Juan Manuel Sepulveda-Sanchez, Timothy F. Cloughesy, Miguel J. Gil-Gil, Vinay K. Puduvalli, Jeffrey J. Raizer, Filip Y. F. De Vos, Patrick Y. Wen, Nicholas A. Butowski, Paul M. J. Clement, Morris D. Groves, Cristobal Belda-Iniesta, Pierre Giglio, Harris S. Soifer, Steven Rowsey, Cindy Xu, Francesca Avogadri, Ge Wei, Susan Moran, Patrick Roth
Summary: The selective FGFR1-3 inhibitor infigratinib showed limited efficacy in patients with FGFR-altered recurrent gliomas, but it may provide durable disease control in patients with tumors harboring FGFR1 or FGFR3 point mutations or FGFR3-TACC3 fusions.
CLINICAL CANCER RESEARCH
(2022)
Review
Gastroenterology & Hepatology
Daniel Walden, Cody Eslinger, Tanios Bekaii-Saab
Summary: Biliary tract cancers, a diverse and aggressive malignancy, have a poor prognosis and limited treatment options. However, advancements in genetic sequencing have opened up new avenues for targeted therapy in this field.
THERAPEUTIC ADVANCES IN GASTROENTEROLOGY
(2022)
Article
Oncology
Anil K. Rengan, Crystal S. Denlinger
Summary: This study describes a case of a female patient with FGFR-aberrant intrahepatic cholangiocarcinoma who had a robust response to futibatinib, even after prior benefit from pemigatinib. The study highlights the safety and efficacy of futibatinib in patients with decompensated cirrhosis and significant cytopenias.
JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK
(2022)
Article
Oncology
Qibiao Wu, Yuanli Zhen, Lei Shi, Phuong Vu, Patricia Greninger, Ramzi Adil, Joshua Merritt, Regina Egan, Meng-Ju Wu, Xunqin Yin, Cristina R. Ferrone, Vikram Deshpande, Islam Baiev, Christopher J. Pinto, Daniel E. McLoughlin, Charlotte S. Walmsley, James R. Stone, John D. Gordan, Andrew X. Zhu, Dejan Juric, Lipika Goyal, Cyril H. Benes, Nabeel Bardeesy
Summary: This study reveals that feedback activation of EGFR signaling limits the effectiveness of FGFR inhibitor therapy and drives adaptive resistance in patient-derived models of FGFR2 fusion-positive cholangiocarcinoma. Inhibition of wild type EGFR can improve the efficacy of FGFR inhibitors and cause tumor regression in vivo, providing a potential improved treatment for patients with FGFR2-driven cholangiocarcinoma.
Article
Oncology
Olaf Neumann, Timothy C. Burn, Michael Allgaeuer, Markus Ball, Martina Kirchner, Thomas Albrecht, Anna-Lena Volckmar, Susanne Beck, Volker Endris, Hannah Goldschmid, Ulrich Lehmann, Huriye Seker-Cin, Sebastian Uhrig, Stephanie Roessler, Jan Budczies, Stefan Froehling, Thomas Longerich, Alex H. Wagner, Arndt Vogel, Peter Schirmacher, Albrecht Stenzinger, Daniel Kazdal
Summary: This study provides a detailed analysis of the genetic characteristics and detection methods of FGFR2 fusion genes in cholangiocarcinoma, as well as suggestions for parameters to be included in molecular diagnostic reports. It aims to support clinicians in decision-making and treatment selection.
BRITISH JOURNAL OF CANCER
(2022)
Article
Oncology
Vishwajith Sridharan, Azfar Neyaz, Abhijit Chogule, Islam Baiev, Stephanie Reyes, Emily G. Barr Fritcher, Jochen K. Lennerz, William Sukov, Benjamin Kipp, David T. Ting, Vikram Deshpande, Lipika Goyal
Summary: This study reveals the frequent overexpression of FGFR mRNA in cholangiocarcinoma in the absence of genetic alterations in FGFR. This has important implications for the treatment of cholangiocarcinoma and further research may lead to breakthrough discoveries.
CLINICAL CANCER RESEARCH
(2022)
Review
Biotechnology & Applied Microbiology
James Yu, Amit Mahipal, Richard Kim
Summary: Cholangiocarcinoma, a highly aggressive cancer, has shown promising clinical benefits with FGFR inhibitors targeting FGFR2 fusions. Infigratinib has been approved by the FDA for cholangiocarcinoma treatment and is currently being evaluated in a Phase 3 trial as a first-line therapy option. Acquired resistance to infigratinib remains a challenge that needs to be addressed in ongoing clinical trials.
ONCOTARGETS AND THERAPY
(2021)
Article
Gastroenterology & Hepatology
Aldo Prawira, Thi Bich Uyen Le, Thanh Chung Vu, Hung Huynh
Summary: Infigratinib has shown promising activity in FGFR-dependent HCC models, but long-term treatment can lead to the development of drug-resistant colonies. This study explored the mechanisms behind infigratinib-induced tumor cell differentiation and resistance, as well as the potential of combining it with the CDK4/6 inhibitor ribociclib to prolong cell differentiation. The combination of FGFR and CDK4/6 pathway inhibition proved to effectively inhibit tumor growth, promote cell differentiation, and reduce drug resistance in HCC. Further clinical investigations in patients with FGFR1-3-dependent HCC are recommended.
LIVER INTERNATIONAL
(2021)
Article
Oncology
Guo-Ming Shi, Xiao-Yong Huang, Tian-Fu Wen, Tian-Qiang Song, Ming Kuang, Hai-Bo Mou, Le-Qun Bao, Hai-Tao Zhao, Hong Zhao, Xie-Lin Feng, Bi-Xiang Zhang, Tao Peng, Yu-Bao Zhang, Xiang-Cheng Li, Hong-Sheng Yu, Yu Cao, Lian-Xin Liu, Ti Zhang, Wei-Lin Wang, Jiang-Hua Ran, Ying-Bin Liu, Wei Gong, Ming-Xia Chen, Lian Cao, Yang Luo, Yan Wang, Hui Zhou, Guo-Huan Yang, Jia Fan, Jian Zhou
Summary: This study evaluated the antitumor activity and safety of pemigatinib in previously treated Chinese patients with advanced cholangiocarcinoma and FGFR2 fusions or rearrangements. The results showed encouraging antitumor activity and favorable safety profile of pemigatinib in patients with FGFR2 rearrangements.
Review
Oncology
Tianyu Wu, Xiaoqing Jiang, Xin Zhang, Bodeng Wu, Bin Xu, Xiaoliu Liu, Lei Zheng, Yu Wang
Summary: This study discusses the application prospects of targeted therapy in iCCA, with FGFR inhibitors showing unique advantages in clinical trials. Results indicate that several effective targeted drugs are currently being used in clinical trials, with promising treatment methods including BGJ398, TASI20, and HSP90 inhibitors.
Article
Pharmacology & Pharmacy
Saeed Sadeghi
Summary: Cholangiocarcinoma is a serious and often late-stage cancer of the liver bile ducts. Current standard treatment involves systemic chemotherapy. Recent research has uncovered gene alterations, leading to the development of targeted therapies. Infigratinib is an oral medication that targets fibroblast growth factor receptor and has received accelerated approval for previously treated patients with advanced or metastatic cholangiocarcinoma.
