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Ivosidenib for Advanced IDH1-Mutated Advanced Cholangiocarcinoma

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Key Points

  • 63% of patients had adverse events that were considered related to ivosidenib; one serious adverse event was considered possibly related to treatment.
  • Four patients (5%) had a partial response to treatment with ivosidenib.
  • Median progression-free survival was 3.8 months. Median overall survival was 13.8 months; however, data were censored for 48 patients (66%).

Ivosidenib, a small-molecule inhibitor of isocitrate dehydrogenase-1 (IDH1), is currently being studied in a phase I clinical trial assessing its efficacy in patients with IDH1-mutated solid tumors. In a report published by Lowery et al in The Lancet Gastroenterology & Hepatology, researchers discuss data from the cholangiocarcinoma cohort of the trial.

The phase I dose-escalation and expansion study of ivosidenib monotherapy in patients with IDH1-mutated solid tumors took place at 12 sites. Patients participating had an IDH1-mutated tumor based on local testing, an ECOG performance status of 0 or 1, one or more previous lines of therapy, and evaluable disease according to Response Evaluation Criteria in Solid Tumors, version 1.1. The primary trial outcomes were safety, tolerability, maximum tolerated dose, and recommended phase II dose.

Ivosidenib was given at 20 to 1,200 mg/d in 28-day cycles in a standard 3+3 design. During the expansion phase, patients received the selected dose based on data from the escalation phase. A total of 73 patients were enrolled into the cholangiocarcinoma cohort between 2014 and 2017.

Results

No dose-limiting toxicities were reported, and maximum tolerated dose was not reached. A dosage of 500 mg/d was selected for expansion.

Four patients (5%) had a partial response to treatment with ivosidenib. Median progression-free survival was 3.8 months (95% confidence interval [CI] = 1.5–13.4). Median overall survival was 13.8 months (95% CI – 11.1–29.3). However, data were censored for 48 patients (66%).

Safety

Adverse events reported in ≥ 20% of patients included fatigue, nausea, diarrhea, abdominal pain, decreased appetite, and vomiting. Grade 3 or worse adverse events reported were ascites (in 5% of patients) and anemia (in 4%); the only treatment-related grade 3 or worse event reported in more than one patient was fatigue, which was reported in two patients (3%).

Two patients had serious adverse events leading to on-treatment death; neither was assessed by the investigator as related to treatment. Sixty-three percent of patients had adverse events that were considered related to ivosidenib; one serious adverse event was considered possibly related to treatment.

The authors concluded, “Ivosidenib might offer a well-tolerated option for patients with IDH1-[mutated] cholangiocarcinoma. An ongoing, global phase III study is evaluating ivosidenib vs placebo in patients with previously treated nonresectable or metastatic IDH1-[mutated] cholangiocarcinoma.”

Disclosure: The study was supported by Agios Pharmaceuticals, Inc. For full disclosures of the study authors, visit thelancet.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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