Cholangiocarcinoma Emerges as Key Target of FGFR Inhibitor Research

Angelica Welch
Published: Wednesday, Dec 19, 2018
Sameek Roychowdhury, MD, PhD
Sameek Roychowdhury, MD, PhD
Recent data have shown that fusions in FGFR1/2/3 can be targetable in many cancers, particularly in cholangiocarcinoma. FGFR inhibitors are now being tested in clinical trials of patients with these fusions.

“I would say that as far as the landscape of FGFR across cancers, we are really only looking at the tip of the iceberg. We really don't know who else is going to have it,” said Sameek Roychowdhury, MD, PhD. “Everyone should be tested for it.”

Findings from 2 studies presented at the 2018 ESMO Congress showed the potential for the FGFR inhibitors infigratinib and pemigatinib in patients with cholangiocarcinoma. Both agents demonstrated favorable safety profiles in their respective studies, as well as signals of antitumor activity. It is still early, however, and the management of adverse events (AEs) is something that needs to be stressed, Roychowdhury said.

In an interview with OncLive®, Roychowdhury, an associate professor at The Ohio State University Comprehensive Cancer Center, discussed the potential for FGFR inhibitors in the treatment of patients with cholangiocarcinoma who harbor FGFR fusions.

OncLive: What is the importance of FGFR inhibitors in cholangiocarcinoma?

Roychowdhury: FGFR gene fusions, sometimes called translocations or rearrangements, have emerged as a significant target for therapy, not only in cholangiocarcinoma, but also in other cancer types. The most common gene fusion in cholangiocarcinoma that is intrahepatic is FGFR2, but we have also seen FGFR1 and FGFR3 in other cancer types, such as urothelial carcinoma, pancreatic cancer, and breast cancer. For each of these cancer types, especially cholangiocarcinoma, early trials involving inhibitors of the FGFR gene, which is a receptor tyrosine kinase, [have] emerged.

There are about 10 FGFR inhibitors in this clinical space being tested in this population who have FGFR fusions. For the most part, we are seeing some promising results. Patients are either having partial responses or rare complete responses. More commonly, we are seeing patients develop stable disease that goes on for quite a long time. We are seeing an improvement in progression-free and probably overall survival. The studies are ongoing.

The most common tumor types where we see [FGFR fusions] are cholangiocarcinoma and urothelial cancer. However, we are seeing this in any solid tumor as a fusion. The frequency of this is low, but it is high enough that it is worthwhile for us to find these patients and offer them therapy, because they have a good chance of benefitting. Over the last couple of years, we have seen patients beyond cholangiocarcinoma and urothelial cancer—including prostate cancer, neuroendocrine tumors, head and neck cancer, breast cancer, and pancreatic cancer—with FGFR-driving genetic alterations. Finding these fusions has allowed patients to qualify for an FGFR inhibitor of some kind and benefit [from it]. As we [do genetic testing on] more and more patients, we are going to find more candidates for testing.

Should FGFR inhibitors be tested in a tumor-agnostic fashion?

As a principle, companies developing and driving FGFR inhibitors are interested in getting these drugs to patients who will benefit. My understanding is that they are interested in patients who have marker-positive cancer, regardless of cancer type. There are definitely disease-specific studies; however, these markers are not limited to patients who have a certain cancer type. We are seeing them in multiple tumor types, and patients are benefitting. The landscape of FGFR drug development isn't limited to 1 or 2 cancer types; any cancer type with a driving alteration in FGFR could be a candidate.

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