The FDA has approved the FGFR2 inhibitor infigratinib for patients with locally advanced or metastatic cholangiocarcinoma who have already been treated for the disease. In a phase II study, the overall response rate for the drug was 23%, and the progression-free survival was 7.3 months. About 77% of patients developed hyperphosphatemia, the most common side effect of the drug.
The FDA has approved infigratinib (Truseltiq; QED Therapeutics) for patients with advanced or metastatic cholangiocarcinoma who have already been treated for the disease. Experts say that doctors will need time to determine how the drug differs from the other recently approved targeted therapy for this cancer, pemigatinib (Pemazyre; Incyte).
Surgery is an option for only about one third of patients with cholangiocarcinoma. For the rest, the standard first-line treatment is chemotherapy with gemcitabine and cisplatin. A second-line therapy, pemigatinib, received accelerated approval from the FDA in 2020 for patients with locally advanced or metastatic tumors that have FGFR2 gene fusions or rearrangements. Between 9% and 14% of patients with cholangiocarcinoma carry these alterations. The decision was notable, says Mitesh Borad, MD, of the Mayo Clinic in Phoenix, AZ, because “it was the first cholangiocarcinoma-specific regulatory approval.”
The supporting data for the pemigatinib's approval came from the FIGHT-202 trial, a single-arm phase II study that included 107 patients with FGFR2 rearrangements or fusions, along with 39 patients with other mutations or no alterations in the fibroblast growth factor pathway (Lancet Oncol 2020;21:671–84). In the patients with FGFR2 rearrangements or fusions, the overall response rate (ORR) was 36%, and the median progression-free survival (PFS) was 6.9 months.
Among all 146 patients in the study, the most common adverse event was hyperphosphatemia, or elevated blood phosphate, which affected 60% of participants. Sixty-four percent of patients suffered side effects that were grade 3 or higher.
The FDA's decision on infigratinib, also an accelerated approval, allows the drug to be used for the same patients as pemigatinib. Both drugs inhibit FGFR2, and their safety profiles and effectiveness are comparable. The data that led to infigratinib's approval came from a single-arm phase II study of 108 patients with FGFR2 rearrangements or fusions. The latest results from this study revealed an ORR of 23% and a median PFS of 7.3 months (J Clin Oncol 39, 2021 [no.3_suppl; abstr 265]). As with pemigatinib, the most common side effect was hyperphosphatemia, which affected 76.9% of patients.
Adding a second targeted therapy for cholangiocarcinoma is a step forward, says Tushar Patel, MB ChB, of the Mayo Clinic in Jacksonville, FL. “It's expanding our therapeutic armamentarium.” Because the drugs are so similar, he says doctors will need more experience with them to determine how best to use each one. In the meantime, he says he would consider both drugs for his patients.
Borad agrees that neither drug has a clear advantage. “In practice, I think people will use them interchangeably.”
Other studies under way could provide more options for cholangiocarcinoma. Separate phase III trials are testing pemigatinib and infigratinib as first-line treatments. And two other FGFR2 inhibitors, futibatinib (Taiho Oncology) and derazantinib (Basilea Pharmaceutica) are in phase II trials for patients with advanced disease or for whom other therapies have not worked. –Mitch Leslie