Clinical Updates on the Treatment of Advanced Cholangiocarcinoma - Episode 18

Implications for Using FGFR Inhibitors in Advanced CCA

April 19, 2021
John L. Marshall, MD, The Ruesch Center for the Cure of GI Cancers

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R. Kate Kelley, MD, UCSF Helen Diller Family Comprehensive Cancer Center

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Sameek Roychowdhury, MD, PhD, James Cancer Hospital & Solove Research Institute

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Milind Javle, MD, MD Anderson Cancer Center

Milind Javle, MD, of The University of Texas MD Anderson Cancer Center, explains what GI oncologists can expect from FGFR treatment for advanced cholangiocarcinoma in terms of treatment responses.

John L. Marshall, MD: Milind, walk us through what the expectation is when you start one of these drugs. You’ve identified a patient with a fusion, you’re in second-line or beyond, and you’re going to start these medicines. What kind of response rates are you seeing? What’s the progression? What’s the data so far?
 

Milind Javle, MD: The only approved agent at this time is pemigatinib, and patients have a very good response rate, about 34% in the second-line setting. These responses are maintained for as long as 7 months. Progression-free survival [PFS] is about 6 months, and overall survival is about 21 months in their study. Then, compare that with what you generally get with FOLFOX in the second-line setting, which is PFS of 4 months and overall survival of 6 months. There’s a lot of excitement, but there’s work to be done because the PFS is still 7, 8 months. We will learn to use these agents sequentially and look at mechanisms so we can get a long-term benefit with several agents.
 

John L. Marshall, MD: Our friend, Ghassan Abou-Alfa et al, published a paper suggesting that FGFR fusions might be a positive prognostic marker. These are patients getting chemotherapy; from this subgroup’s data set, we see that they are back to good overall survival. Anybody have thoughts on whether that’s true, or is this the early look?
 

Milind Javle, MD: There have been several papers in this field—1 from our group, 1 from Dr Goyal’s group, and now 1 from Dr Abou-Alfa’s group—showing that FGFR fusion cases are often a different clinical phenotype. They have more indolent disease, longer survival, earlier stages of presentation—more in women than in men—and there’s also a subgroup of patients who are less than 40. There’s more of a younger dominance in this subgroup.
 

R. Kate Kelley, MD: This is where it gets hard to flesh out the significance of prognostic vs predictive biomarkers. A lot of these data come from centers that identify patients in the context of a clinical trial, so a lot of the patients ended up getting a very active drug. We need natural history registries to study this, to try to flesh out the impact of drug impacting prognosis, ie, a predictive value vs true prognosis.
 

John L. Marshall, MD: I read that abstract closely to see if I could answer that, the percentage of patients receiving the targeted therapy, and I didn’t see it. It’s small print. I couldn’t agree more with you, though. Is infigratinib much different than pemigatinib? How are their mechanisms are different?
 

Milind Javle, MD: All of us here were involved in the trial that was presented at ASCO GI [American Society of Clinical Oncology Gastrointestinal Cancers Symposium] a couple of months ago. Infigratinib is an ATP-competitive inhibitor, very specific for FGFR1 to 3. It has much less FGFR4 activity compared with some of the other agents, such as pemigatinib and futibatinib, and it’s very potent for FGFR2. This has been investigated, and it’s completed the pivotal phase 2 trial and is awaiting FDA approval. We’re hopeful.
 

John L. Marshall, MD: We may soon have 2 drugs on the market in this space.

TRANSCRIPT EDITED FOR CLARITY