The FDA approved ivosidenib as the first targeted therapy to treat patients with previously treated IDH1-mutated cholangiocarcinoma.
The FDA approved ivosidenib (Tibsovo) for the treatment of previously treated, locally advanced or metastatic cholangiocarcinoma with an IDH1 mutation, as detected by an FDA-approved test, in adult patients.
The regulatory decision is based on findings from the phase 3 ClarlDHy study, which showed a statistically meaningful improvement in progression-free survival (HR, 0.37; 95% CI, 0.25-0.54; P < .001), which was determined by an independent review committee. Six- and 12-month PFS was 32% and 22%, respectively, in the ivosidenib arm. In comparison, no patients on the placebo arm were free of progression at either of these time markers.
"Patients living with IDH1-mutated cholangiocarcinoma, especially those whose disease progresses following chemotherapy, are in urgent need of new treatment options," said Rachna T. Shroff, MD, associate professor of medicine, University of Arizona, and chief of GI medical oncology at the University of Arizona Cancer Center, in a press release. "In addition to an acceptable safety profile, Tibsovo demonstrated an impressive, significant benefit in progression-free survival, underscoring its importance as a new option for patients battling this aggressive cancer."
Notably, the study design allowed patients in the placebo cohort to switch to the experimental group if their disease progressed. The majority of patients (70.5%) in the placebo cohort ultimately switched to ivosidenib treatment. Overall survival (OS) was based on a final analysis 16 months after the first assessment of PFS. At 16 months, the median OS was 10.3 months in the experimental arm (95% CI, 7.8-12.4) and 7.5 months in the control arm (95% CI, 4.8-11.1).
Adverse events (AEs) were consistent with previously reported data. The most common AEs included fatigue, nausea, abdominal pain, diarrhea, cough, decreased appetite, ascites, vomiting, anemia, and rash. Over 15% of patients reported one of these AEs.
The recommended dosage for ivosidenib is 500 mg orally once daily with or without food. Treatment should be stopped if disease progresses or if unacceptable toxicity occurs.
"Before today's approval of Tibsovo, there were no approved targeted therapies available to cholangiocarcinoma patients harboring the IDH1 mutation, and limited chemotherapy options available to patients with advanced disease," said Stacie Lindsey, Founder and CEO, Cholangiocarcinoma Foundation, in a press release. "This approval brings new hope to the cholangiocarcinoma community and we are excited that this much-needed new therapeutic option is being made available to patients."
Servier announces FDA approval of TIBSOVO® (ivosidenib tablets) in IDH1-Mutated cholangiocarcinoma. Cision. News release. Accessed August 25, 2021. https://www.prnewswire.com/news-releases/servier-announces-fda-approval-of-tibsovo-ivosidenib-tablets-in-idh1-mutated-cholangiocarcinoma-301363055.html