In April 2020, pemigatinib received FDA approval for locally advanced or metastatic cholangiocarcinoma with FGFR2 gene fusion [1], becoming the first targeted drug for cholangiocarcinoma. In addition to cholangiocarcinoma, pemigatinib is also entering other solid tumors and may become a new pan-cancer target medicine. Recently, V. Subbiah of MD Anderson Cancer Center published a paper announcing the results of the FIGHT-101 study [2]. In this study, 128 patients with multiple advanced solid tumors who had failed prior therapy were treated with pemigatinib, and partial responses were observed in multiple cancer types, including cholangiocarcinoma. 
Pemigatinib is a fibroblast growth factor receptor ( FGFR) inhibitor. FGFR is involved in the regulation of many physiological processes in the human body, such as embryonic development, cell differentiation, proliferation and migration, angiogenesis, etc., including four molecules of the same family of FGFR1~4. In cancer, in addition to being an important tumor driver mutation, FGFR can also promote tumor angiogenesis and help tumors develop resistance to some anticancer drugs[3]. According to statistics, about 7.1% have FGFR gene abnormalities, including FGFR gene amplification, activating mutation and gene fusion [4]. likeurothelial, breast, endometrial, bile duct cancers, etc., all of which are cancers with more FGFR gene mutations. In cholangiocarcinoma, the FGFR inhibitor pemigatinib achieved an objective response rate of 36% and has been approved by the FDA. Is pemigatinib effective in other FGFR-mutated cancers? 
Proportions of FGFR variants in different cancer types A total of 128 patients with advanced cancer who had progressed after treatment and had no available therapy were included and divided into two treatment groups, 70 and 58 in continuous dosing and intermittent dosing, respectively. The median age of these patients was 59 years, 78% were women, and the cancers included bile duct cancer, breast cancer, colon cancer, lung cancer, etc., and 76.6% had received at least 3 failed rounds of treatment. In the trial, 12(9.4%)< span>Patients with partial remission after pemigatinib treatment, 40 patients(31.3%)stable disease, 49 patients(38.3%) Progressive disease, and 27 others were not evaluated for efficacy. The 12 patients with partial responses included five patients with cholangiocarcinoma, and one each with head and neck cancer, pancreatic cancer, gallbladder cancer, uterine cancer, urothelial cancer, fibrous astrocytoma, and non-small cell lung cancer. Of the total 128 patients, 96 had available FGF/FGFR gene data, and 79 of them carried FGF/FGFR gene variants, including 20 FGFR gene fusions or reassortments. Row, 13 FGFR activating mutations, 26 FGFR amplifications, and 20 FGF amplifications. 10 of the 79 patients with FGF/FGFR gene variants had a partial response, and the objective response rate was 12.7%. Among them, patients with FGFR gene fusion or rearrangement had the highest objective response rate of 25%. Followed by patients with FGFR activating mutations, the objective response rate was 23.1%. Patients with FGFR amplification and FGF amplification had lower objective response rates, 3.8% and 5%, respectively. 
Objective response rate in patients with different FGF/FGFR variant types in the studyMainly emerging treatments in the study Related adverse reactions include dry eye, eyelash changes, hyperphosphatemia, hypophosphatemia, nail toxicity, blurred vision, etc. Among them, the incidence of serious adverse reactions of grade 3 and above in the intermittent dosing group was 50% , significantly lower than the 75.9% of the continuous administration group.This study once again demonstrated the effectiveness of pemigatinib in cholangiocarcinoma, in other patients with FGF/ FGFR-mutated cancers have also shown some activity and may become a new pan-cancer targeted drug.
References:[1]. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-pemigatinib-cholangiocarcinoma-fgfr2-rearrangement -or-fusion[2]. Subbiah V, Iannotti NO, Gutierrez M, et al. FIGHT-101, a first-in-human study of potent and selective FGFR 1–3 inhibitor pemigatinib in pan -cancer patients with FGF/FGFR alterations and advanced malignancies[J]. Annals of Oncology, 2022.[3]. Touat M, Ileana E, Postel-Vinay S, et al. Targeting FGFR signaling in cancer[J]. Clinical cancer research, 2015, 21(12): 2684-2694.< span>[4]. Helsten T, Elkin S, Arthur E, et al. The FGFR landscape in cancer: analysis of 4,853 tumors by next-generation sequencing[J]. Clinical Cancer research, 2016, 22(1): 259- 267.