Dr Bekaii-Saab on First-Line Pemigatinib in FGFR2-Rearranged Cholangiocarcinoma

"Across the board, PFS rate, response rate, and duration of response were all significantly improved... this remains the largest study ever to report first-line activity for an FGFR inhibitor [in CCA] period."

Tanios S. Bekaii-Saab, MD, FACP, the David F. and Margaret T. Grohne Professor of Novel Therapeutics for Cancer Research I at Mayo Clinic College of Medicine and Science; the division chair of Hematology/Medical Oncology at Mayo Clinic; the co-leader of the Advanced Clinical and Translational Science Program; and the disease group leader for Gastrointestinal Cancers for the Mayo Clinic Comprehensive Cancer Center, discussed results from the phase 3 FIGHT-302 trial (NCT03656536), which evaluated frontline pemigatinib (Pemazyre) vs gemcitabine plus cisplatin in patients with unresectable, locally advanced, or metastatic cholangiocarcinoma (CCA) harboring FGFR2 rearrangements.

Data presented at the 2026 ASCO Annual Meeting demonstrated that pemigatinib significantly prolonged the primary end point of progression-free survival (PFS) to a median of 8.34 months (95% CI, 6.51-12.22), compared with 6.80 months (95% CI, 6.05-8.25) in the chemotherapy arm (HR, 0.584; 95% CI, 0.393-0.868; P = .0078). The targeted agent provided a nearly threefold increase in objective response rate over chemotherapy (47.0% vs 15.5%) and a significantly longer duration of response at 14.2 months (95% CI, 8.7-24.7) vs 6.3 months (95% CI, 4.3-not estimable) with chemotherapy. The respective disease control rates were 89.2% and 67.9% (OR, 4.10; P = .0007).

The median overall survival (OS) was similar between arms, with a median OS of 24.4 months (95% CI, 18.6-35.9) for pemigatinib vs 25.0 months (95% CI, 18.7-34.2) with gemcitabine plus cisplatin (HR, 1.095; 95% CI, 0.733-1.637; P = .6581); Bekaii-Saab attributed this to high rates of treatment crossover. Approximately 50% of patients in the chemotherapy group transitioned to pemigatinib, and another 30% received subsequent FGFR inhibitors, such as futibatinib (Lytgobi). Notably, the small subset of patients who never received an FGFR inhibitor during their care had a significantly shorter median OS of 11.1 months.

Bekaii-Saab acknowledged the hurdles of the study, including genomic testing delays and a shifting standard of care that added PD-1/PD-L1 inhibitors such as durvalumab (Imfinzi) or pembrolizumab (Keytruda) to chemotherapy. Despite these complexities leading to early stoppage, he emphasized that FIGHT-302 remains the largest study to report frontline activity for an FGFR inhibitor. These findings underscore the superior efficacy and durability of targeted therapy over traditional chemotherapy in this molecularly defined subset of CCA.

This video was supported in part by Incyte. Content independently developed and published by OncLive.