Cholangiocarcinoma Drug Pulled From Market, Other Options Still Viable


While the FDA approval of Truseltiq for FGFR2-positive cholangiocarcinoma was withdrawn, there are still other viable treatment options, an expert said.

Image of cholangiocarcinoma.

Truseltiq, a treatment for certain patients with cholangiocarcinoma, was withdrawn from the American market.

The Food and Drug Administration (FDA) approval of Truseltiq (infigratinib) for patients with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma (bile duct cancer) that harbored an FGFR2 fusion or rearrangement, was recently withdrawn from the American market after researchers were unable to recruit enough patients for a trial to confirm the drug’s benefit.

However, one expert assured that patients with the disease have other treatment options that may work just as well.

“The number of patients who are on [Truseltiq] is actually quite small,” Dr. Juan Valle, chief medical officer at the Cholangiocarcinoma Foundation, said in an interview with CURE®.

Other Treatment Options

Valle mentioned that another drug, Pemazyre (pemigatinib), is also approved for this patient population. This drug was approved in April 2020 after data from the FIGHT-202 trial showed that 36% of patients responded to treatment (meaning that their disease shrunk or disappeared) with Pemazyre, including three patients who achieved a complete response, meaning that cancer became undetectable.

Image of data regarding three drugs for cholangiocarcinoma.

Data comparison of the three drugs and their response rates in patients with cholangiocarcinoma with FGFR2 fusions or rearrangements.

Additionally, in September 2022, the FDA approved Lytgobi (futibatinib) for cholangiocarcinoma with FGFR2 gene fusions or other rearrangements. This approval was based on data from the TAS-120-101 trial that showed 42% of patients responded to treatment. Then, the FOENIX-CCA2 trial confirmed the benefit of this drug.

“The activity of this drug, in terms of how effective it is, is very similar between the two drugs (Truseltiq and Pemazyre),” Valle said. “So for patients who are on [Truseltiq] and can no longer get [it], they could safely switch them to an alternative, either [Pemazyre] or even one of the newer-generation [drugs] called [Lytgobi].”

Difficulty Completing a Confirmatory Trial

The FDA approval of Truseltiq was backed by findings of the single-arm phase 2 CBGJ398X2204 clinical trial, which showed that 23% of patients responded to therapy, including one complete response — that, according to Valle — is “more than what we’re seeing with chemotherapy.”

“So as a standalone phase 2 study, it looked very promising and on the basis of that, the FDA granted its initial accelerated approval,” Valle said. “When you get an accelerated approval, [the pharmaceutical company] then has to follow up with a second study — usually in a randomized setting — to be able to confirm what you see in a singular-arm phase 2 study.”

Single-arm studies, such as CBGJ398X2204, are trials where all patients receive the same therapy. Randomized trials, on the other hand, randomly assign patients to groups that each have different treatment regimens. In doing so, the researchers can directly compare outcomes of separate therapies.

Helsinn Healthcare, the pharmaceutical company collaborating with QED Therapeutics to develop Truseltiq, reported difficulties enrolling enough patients in PROOF, the randomized phase 3 clinical trial comparing Truseltiq with standard-of-care gemcitabine plus cisplatin.

Cholangiocarcinoma is a rare type of cancer, with approximately 8,000 people in the United States receiving a diagnosis each year, according to the American Cancer Society. FGFR2 fusions or rearrangements are even rarer and occur in up to 14% of patients with intrahepatic (inside the liver) cholangiocarcinoma, per research published in 2023 in The New England Journal of Medicine.

“Showing a similar magnitude of benefits, all of the [pharmaceutical companies of drugs approved for FGFR2-positive cholangiocarcinoma] were given the advice of having a major study by the FDA, such that at one point there were going to be three randomized-controlled trials comparing the FGFR2 inhibitors to chemotherapy,” Valle said. “They needed thousands of patients to complete that study, and it was just never going to happen.”

Optimism Remains as Cholangiocarcinoma Becomes the ‘Poster Child’ for Targeted Therapy

Even though cholangiocarcinoma is a rare cancer, Valle said that he is still optimistic about the future of the disease, especially as it pertains to more personalized therapies.

“We are very excited about the identification of these molecular subgroups. FGFR2 is not the only one. The list is growing, and, in fact, cholangiocarcinoma is becoming the poster child for targeted therapies and biomarker-driven therapies,” he said.

The Cholangiocarcinoma Foundation had its annual conference in April, which included a session about the regulatory approval processes for rare cancers and even rarer subgroups of these cancers. Valle said that while the need for a confirmatory study is “very valid,” perhaps the data can be collected in some way other than a randomized trial.

“We’re considering where can we get that data from, other than a randomized controlled trial? One is the design of the trial — a trial can be looking at different dosing strategies within a randomized setting, but also be able to access real-word data (data of patients not being treated on a trial) or external controls,” he said. “That leads to the question of what the quality of data has to be when we’re using those out-of-trial data sources.”

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