Ivosidenib is a first-in-class inhibitor of IDH1 mutation that is indicated for the treatment of previously treated, locally advanced or metastatic cholangiocarcinoma (CCA) and IDH1 mutation. This indication was approved based on the results of the phase 3 ClarIDHy clinical trial, which demonstrated significant improvement in progression-free survival with ivosidenib compared with placebo in patients with previously treated, unresectable or metastatic CCA harboring IDH1 mutations.1,2
At the 2022 ASCO GI Cancers Symposium, Christina X. Chamberlain, PhD, of Servier Pharmaceuticals, Boston, MA, presented the results of a longitudinal assessment of health-related quality of life (QOL) in ivosidenib-treated patients enrolled in the ClarIDHy study.
The eligibility criteria in the ClarIDHy study included unresectable or metastatic CCA, centrally confirmed IHD1 mutations by next-generation sequencing, measurable disease, and use of 2 previous therapies. Eligible patients were randomized (2:1) to ivosidenib (500 mg once daily in continuous 28-day cycles) or to placebo. The study design allowed crossover from the placebo to the ivosidenib arm at radiographic progressive disease. Health-related QOL was a secondary end point of the study.
The QOL was assessed before dosing on cycle 1, day 1, every 4 weeks on the first day of subsequent cycles, and every 12 weeks thereafter, until the start of a new anticancer therapy. QOL assessments were done using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and the Cholangiocarcinoma and Gallbladder Cancer module (QLQ-BIL21) instruments; the prespecified domains of interest were physical functioning, pain, and appetite loss. A 12 to 13 point score decrease was estimated to be the threshold for clinically meaningful decline in the EORTC QLQ-C30 physical functioning subscale, and 10-point decline was the threshold for other assessments.
At baseline, EORTC QLQ-C30 scores were available for 114 patients in the ivosidenib group and 53 patients in the placebo group; QLQ-BIL21 scores were available for 108 patients receiving ivosidenib and 52 patients receiving placebo. Over time, the sample sizes for the QOL analyses decreased in both arms, with no QOL assessments available for the placebo cohort after cycle 8 (ie, week 28), and EORTC QLQ-C30 change in scores were available for 17 patients in the ivosidenib cohort at week 52.
From baseline to cycle 27, day 1, patients who continued with ivosidenib therapy maintained their QOL. No changes in scores from baseline that exceeded the 12 to 13 threshold were seen in those receiving ivosidenib on the EORTC QLQ-C30 physical functioning subscale; by contrast, deterioration of clinically meaningful physical functioning was observed after baseline at multiple cycles in the placebo group. In terms of the EORTC QLQ-C30 pain and appetite loss and the QLQ-BIL21 pain and eating subscales, the preservation of QOL among ivosidenib-treated patients was similar to that observed with the EORTC QLQ-C30 physical functioning.
Based on results of the ClarIDHy study, Dr Chamberlain and colleagues concluded that patients with advanced CCA harboring IDH1 mutations who received treatment with ivosidenib maintained their QOL over the duration of treatment.
Chamberlain CX, Hua Z, Gliser C, et al. Longitudinal trends in health-related quality of life (HRQoL) among patients treated with ivosidenib (IVO) for IDH1-mutated cholangiocarcinoma (CCA) in the ClarIDHy study. Abstract 388.
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