Biliary tract cancer refers to cancer that occurs in the bile duct that connects the liver and gallbladder to the small intestine, and is largely divided into intrahepatic bile duct cancer and extrahepatic bile duct cancer depending on the location of the occurrence. Most of the extrahepatic bile duct cancer is 90%, and the rest of the intrahepatic bile duct cancer is about 10%. The 5-year survival rate of all bile duct cancer patients is only 9-10%, and stage 4 bile duct cancer is extremely poor at 2%.
 

Mutations such as the fusion of the FGFR2 gene have been found in 13-17% of patients with intrahepatic bile duct cancer, and new drugs targeting them have recently been developed and approved.
 

The first licensed drug is Insight Pharmaceutical Company's Femigatinib (PEMAZYRE), licensed by the U.S. Food and Drug Administration (FDA) on April 17, 2020, for patients with unresectable or metastatic biliary tract cancer who have mutations such as the fusion of the FGFR2 gene and have previously been treated, and has pointed to FoundationOne CDX testing as a companion diagnostic method. Behind this approval was the results of the FIGHT-202 clinical trial. In the FIGHT-202 study, femigatinib 13.5 mg was administered orally once daily for two weeks and took a week off in 107 patients with advanced and metastatic biliary tract cancer with mutations such as fusion of the FGFR2 gene. The response rate was observed at 36%, and the median duration of the response was about 9 months. The main side effects were hair loss, diarrhea, fatigue, nausea, constipation, stomatitis, dry skin, nail deformation, joint pain, and muscle pain, and abnormalities were also observed in the cornea.
 

The second authorized drug is QED Pharmaceutical Company's Infigratinib (Truseltiq), which was authorized by the U.S. Food and Drug Administration on May 28, 2021, for patients with unresectable or metastatic biliary tract cancer who have mutations such as the fusion of the FGFR2 gene and have previously been treated, and has also pointed to the FoundationOne CDX test as a companion diagnostic method. Behind this approval was the results of the CBGJ398X2204 clinical trial. The CBGJ398X2204 study performed a three-week orally daily dose of 125 mg of infigratinib for three weeks and a one-week break in 108 patients with advanced and metastatic biliary tract cancer with mutations such as fusion of the FGFR2 gene. The response rate was observed at 23%, and the median duration of the response was about 5 months. The main side effects were dry eyes, fatigue, nausea, constipation, stomatitis, dry skin, nail deformation, joint pain, and muscle pain, and tests and ophthalmic examinations for increased phosphorus concentration in the blood were recommended.
 

The third licensed drug is Japan's Daiho Pharmaceutical Company's Lytgobi, authorized by the U.S. Food and Drug Administration on Sept. 30, 2022, for patients with unresectable or metastatic intrahepatic bile duct cancer who have mutations, including the fusion of the FGFR2 gene, and have previously been treated. Behind this approval was the results of the TAS-120-101 clinical trial. The TAS-120-101 study was conducted in 103 patients with advanced and metastatic intrahepatic bile duct cancer with mutations, such as fusion of the FGFR2 gene, until they discontinued due to progression of cancer or side effects. The response rate was observed in 42%, and the median duration of the response was about 9.7 months. The main side effects were nail deformation, musculoskeletal pain, fatigue, nausea, constipation, diarrhea, stomatitis, dry skin, stomatitis, and hair loss.
 

Treatment for biliary tract cancer patients is making a lot of progress, and the scope of precision medical care is gradually expanding. Patients diagnosed with advanced or metastatic biliary cancer, especially intrahepatic bile duct cancer, must check for mutations such as the fusion of the FGFR2 gene and check if they can participate as various pharmaceutical companies are still conducting clinical trials of new drugs targeting mutations such as the fusion of the FGFR2 gene.