Ivosidenib Approved for Advanced or Metastatic Cholangiocarcinoma

The FDA has approved ivosidenib for adult patients with previously treated, locally advanced or metastatic cholangiocarcinoma (CCA) with an isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test.

The FDA also approved the Oncomine Dx Target Test as a companion diagnostic device to assist in selecting patients with CCA for treatment with ivosidenib.

The approval was based on results from a phase 3, multicenter, randomized, double-blind, placebo-controlled trial in which 185 adult patients with locally advanced or metastatic CCA with an IDH1 mutation, who had received 1 to 2 prior treatment regimens (including ≥1 gemcitabine- or 5-fluorouracil–containing regimens), were treated with once-daily 500-mg ivosidenib or placebo until disease progression or unacceptable toxicity.

For the trial, the primary end point was progression-free survival (PFS) as determined by an independent review committee according to RECIST version 1.1. The results indicated a statistically significant improvement in PFS for patients randomized to ivosidenib (hazard ratio [HR], 0.37; 95% confidence interval [CI], 0.25-0.54; P <.0001). The analysis of overall survival was not significant (HR, 0.79; 95% CI, 0.56-1.12; P = .093). Seventy percent of patients randomized to placebo had crossed over to receive ivosidenib after radiographic disease progression.

In a news release from Servier Pharmaceuticals that accompanied the approval of ivosidenib, CCA News editorial advisory board member Rachna T. Shroff, MD, Associate Professor of Medicine, University of Arizona, and Chief of GI Medical Oncology at the University of Arizona Cancer Center, said that, in addition to having an acceptable safety profile, ivosidenib “demonstrated an impressive, significant benefit in progression-free survival, underscoring its importance as a new option for patients battling this aggressive cancer.”

The most common adverse reactions (occurring in ≥15% of patients with CCA) were fatigue, nausea, abdominal pain, diarrhea, cough, decreased appetite, ascites, vomiting, anemia, and rash.