FGFR Inhibitors in Oncology: Insight on the Management of Toxicities in Clinical Practice

Cancers

Milind Javle¹  Mitesh Borad²  Sri Harsha Tella³  Anuhya Kommalapati³  Amit Mahipal³ 

[1] Department of Gastrointestinal Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;Department of Medical Oncology, Mayo Clinic, Phoenix, AZ 85259, USA;Department of Medical Oncology, Mayo Clinic, Rochester, MN 55905, USA;

关键词: FGFR;    hyperphosphatemia;    urothelial carcinoma;    cholangiocarcinoma;    pemigatinib;    erdafitinib;   

DOI  :  10.3390/cancers13122968

来源: DOAJ

【 摘 要 】

Fibroblast Growth Factor receptor (FGFR) pathway aberrations have been implicated in approximately 7% of the malignancies. As our knowledge of FGFR aberrations in cancer continues to evolve, FGFR inhibitors emerged as potential targeted therapeutic agents. The promising results of pemigatinib and infigratinib in advanced unresectable cholangiocarcinoma harboring FGFR2 fusions or rearrangement, and erdafitinib in metastatic urothelial carcinoma with FGFR2 and FGFR3 genetic aberrations, lead to their accelerated approval by the United States (USA) FDA. Along with these agents, many phase II/III clinical trials are currently evaluating the use of derazantinib, infigratinib, and futibatinib either alone or in combination with immunotherapy. Despite the encouraging results seen with FGFR inhibitors, resistance mechanisms and side effect profile may limit their clinical utility. A better understanding of the unique FGFR-inhibitor-related toxicities would invariably help us in the prevention and effective management of FGFR-inhibitor-induced adverse events thereby enhancing their clinical benefit. Herein, we summarized the physiology of FGF/FGFR signaling and briefly discussed the possible mechanisms that could lead to FGFR inhibitor resistance and side effects. In addition, we proposed treatment guidelines for the management of FGFR-inhibitor-associated toxicities. This work would invariably help practicing oncologists to effectively manage the unique toxicities of FGFR inhibitors.

【 授权许可】

Unknown