‘Landmark’ FDA Approval of Tibsovo May Improve Outcomes for Liver Cancer Subtype


The FDA approval of Tibsovo marks the first targeted therapy for patients with this liver cancer subtype.

Patients who receive a diagnosis of cholangiocarcinoma with an IDH1 mutation may have better survival outcomes thanks to the recent Food and Drug Administration’s (FDA) approval of Tibsovo (ivosidenib).

The approval, which is based off of findings from the randomized phase 3 ClarIDHy trial, is the first targeted therapy for patients who receive a diagnosis of cholangiosarcoma with an IDH1 mutation. It also marks the third drug to be approved for patients with the disease in general. About 20% of cholangiocarcinoma cases have the mutation, according to Dr. Rachna T. Shroff, who was a researcher on the trial, “which is not all of the population, but it's actually a significant chunk of this population.”

“This is a landmark approval. This is a disease that, for the longest time, we had no FDA-approved therapies,” said Shroff, an associate professor of medicine at the University of Arizona and chief of GI medical oncology at the University of Arizona Cancer Center in Tucson, in an interview with CURE®. “It is in the setting of a locally advanced and metastatic disease, it carries a dismal prognosis and, historically, even though there are 8,000 cases of cholangiocarcinoma a year, it was treated almost like an orphan disease with very little interest in terms of drug development.”

Findings from the trial demonstrated statistically significant improvement in progression-free survival (time during and after treatment when the patient lives without disease worsening) with Tibsovo (2.7 months) compared with placebo (1.4 months). The most common side effects reported were fatigue, nausea, abdominal pain, diarrhea, cough, decreased appetite, vomiting, anemia, rash and ascites (abdominal swelling caused by an accumulation of fluid).

“Tibsovo is actually a very well-tolerated therapy. … I can't even tell you how happy patients were to be on a pill and to not have IV chemo,” Shroff said. “I think it's important to point out that a lot of the side effects that patients were talking about are side effects that also come from this disease, from cholangiocarcinoma. So abdominal pain, ascites (excess abdominal fluid), I mean, these are things that, unfortunately, a lot of our patients live with.”

She added that having the option of taking a pill rather than IV chemo or FOLFOX (a regimen of three chemotherapy drugs: folinic acid, fluorouracil and oxaliplatin) also seemed to help patients both psychologically and emotionally. “It's just so much more palatable to take a pill,” she said.

The approval of Tibsovo highlighted the importance of biomarker testing, according to Shroff. Before the approval, those patients who received a diagnosis of cholangiocarcinoma with an IDH1 mutation were treated similarly to a patient without the mutation. This involved combination chemotherapy of gemcitabine and cisplatin in the frontline setting — all of which had low response rates and low progression-free survival. “It speaks to the importance of doing biomarker testing on every single cholangiocarcinoma patient. I cannot underscore that enough to patients to advocate for that, and to providers to know that we should be doing this at this point,” she explained, adding that knowing if a patient has an IDH1 mutation can help to better plan for second- and third-line settings.

While Shroff added that the IDH1 mutation is not necessarily prognostic when it comes to predicting patient outcomes on specific treatments, she noted that knowing that the mutation responds to a targeted therapy is a huge step forward.

“As completely cheesy as it sounds, I was tearing up when this approval came through last week, because in January of 2020, we had zero drugs FDA approved for this disease, and we have three now,” she said of cholangiocarcinoma. “And that's just unbelievable to see and to think about what that means for our patients.”

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