Rachna T. Shroff, MD
Invited study discussant Rachna T. Shroff, MD, Associate Professor of Medicine, University of Arizona, and Chief of GI Medical Oncology at the University of Arizona Cancer Center, said the study presented by Dr. Javle1 showed the FGFR2 inhibitor infigratinib to be active in FGFR2 fusion–positive cholangiocarcinoma. She added: “I strongly feel it mostly hits the mark … especially when you look at patients receiving it in earlier lines of therapy…. Most patients had some benefit from infigratinib, and there is a 7.3-month progression-free survival, which is impressive in a pretty refractory patient population.”
These outcomes are also in line with recently reported data for two other FGFR2 inhibitors—pemigatinib and futibatinib. Moreover, she pointed out, the infigratinib population was more heavily pretreated than those receiving pemigatinib in the phase II FIGHT-202 trial,2 where 61% had received one prior line compared with 46% of the patients given infigratinib and 45% of the patients receiving futibatinib in the FOENIX-CCA2 trial.3
Dr. Shroff acknowledged there are side effects with infigratinib that could result in cumulative toxicity. Since progression-free survival is prolonged, it will be important to see whether they decrease tolerance and compliance, she said. “However, over time, we are learning how to manage these adverse events, so patients can continue on these drugs without significant toxicity,” she added.
With several FGFR2 inhibitors becoming available, a next step is to learn how to sequence them, and this will require a better understanding of resistance, commented Dr. Shroff. Another question will be to determine the benefit of infigratinib in the front-line setting, “given that it seems to do better in earlier lines,” she added. “Is there a role for it in lieu of gemcitabine/cisplatin?” Phase III studies of these agents, including the PROOF trial of infigratinib, hope to answer this question.
Another Perspective
“In addition to the efficacy and safety data, I think we also need to consider the relevance of this study in how it impacts our approach to cholangiocarcinoma as a disease,” said Gentry King, MD, Assistant Professor, University of Washington, in comments to The ASCO Post. “This is another study that further solidifies precision oncology as a feasible and valid therapeutic strategy for cholangiocarcinoma. Though we have known about the rich molecular heterogeneity of cholangiocarcinoma for the past few years, we are now finally seeing this translate into truly relevant therapeutic subtypes.”
Gentry King, MD
Dr. King continued: “We also have to consider the therapeutic landscape to which infigratinib might be entering. How will it compare to other selective inhibitors?”
DISCLOSURE: Dr. Shroff has served as a consultant or advisor to Agios, AstraZeneca, Boehringer Ingelheim, Clovis Oncology, Debio Pharma, Exelixis, Incyte, Merck, QED Therapeutics, Seattle Genetics, and Taiho Pharmaceutical and has received research funding from Agios, Exelixis, Halozyme, Merck, Pieris Pharmaceuticals, QED Therapeutics, Rafael Pharmaceuticals, and Taiho Pharmaceutical. Dr. King reported no conflicts of interest.
REFERENCES
1. Javle MM, et al: Final results from a phase II study of infigratinib (BGJ398), an FGFR-selective tyrosine kinase inhibitor, in patients with previously treated advanced cholangiocarcinoma containing FGFR2 fusions/rearrangements. 2021 Gastrointestinal Cancers Symposium. Abstract 265. Presented January 17, 2021.
2. Abou-Alfa GK, et al: Pemigatinib for prevoiusly treated, locally advanced or metastatic cholangiocarcinoma. Lancet Oncol 21:671-684, 2020.
3. Goyal L, et al: FOENIX-CCA2: A phase II, open-label, multicenter study of futibatinib in patients with intrahepatic cholangiocarcinoma harboring FGFR2 gene fusions or other rearrangements. ASCO20 Virtual Scientific Program. Abstract 108.
