Ivosidenib Maintains Quality of Life in Patients With Cholangiocarcinoma

Ivosidenib Maintains Quality of Life in Patients With Cholangiocarcinoma

Ivosidenib (Tibsovo) was linked to a promising preservation of health-related quality of life (HRQOL) among patients with advanced chemotherapy-refractory cholangiocarcinoma and an IDH1 mutation, according to a long-term follow-up of the ClarIDHy study (NCT02989857).¹ The data were presented at the 2022 Gastrointestinal Cancers Symposium.

Investigators specifically assessed how the oral agent impacted patients’ physical function, pain, and appetite loss compared with placebo. In terms of physical function, the changes between baseline and 27 days of treatment did not reach the prespecified 12- to 13-point threshold—marking a lack of clinically meaningful decline among those treated with ivosidenib.

Patients receiving placebo, however, demonstrated clinically meaningful deterioration across multiple cycles. Similarly, for pain, appetite loss, and eating, the least square means of change were reported for patients receiving ivosidenib compared with those on placebo.

“Cholangiocarcinoma is a rare and aggressive cancer and treatment options are primarily limited to chemotherapy. Mutations in the IDH1 protein have been found to occur in approximately 1 to 3% of intrahepatic cholangiocarcinomas and 1% of extrahepatic cholangiocarcinomas globally,” Christina X. Chamberlain PhD, of Servier Pharmaceuticals LLC, explained in a presentation of the findings.

“Overall, patients who remain on ivosidenib tend to maintain their health-related quality of life based on the least squares mean changes over time from baseline through cycle 27, day 1, which corresponds approximately to year 2,” she added.

Ivosidenib is an oral, targeted agent which functions by inhibiting the mutant IDH1 protein. The drug was approved by the FDA in August 2021 for use in this patient population, based on findings from the ClarIDHy trial (NCT02989857).²

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.

ClarIDHy was a randomized, double-blind, placebo-controlled, phase 3 trial, which assessed the agent’s efficacy in previously treated patients with cholangiocarcinoma and an IDHI mutation. Participants needed to have at least 1 but no more than 2 prior treatments for advanced disease (nonresectable or metastatic), gemcitabine or a fluorouracil-based chemotherapy regimen. Patients could not enroll if they had already received an IDH1 inhibitor.³

The study enrolled participants from 49 hospitals across 6 countries; the research period extended from February 20, 2017 to May 31, 2020. Eligible participants were 18 years or older and the median age was 62 years.

The poster at the 2022 Gastrointestinal Cancers Symposium highlighted findings from a longitudinal assessment of HRQOL related to the ClarIDHy study. At the data cutoff of May 31, 2020, a total of 187 patient had been randomized to ivosidenib (n = 126) or placebo (n = 61). In the instance of confirmed radiographic disease progression, patients in the placebo arm were permitted to switch to ivosidenib.

Of note, 48 of the 61 patients on placebo ultimately switched over to ivosidenib following disease progression determined by radiographic findings.

Primary outcomes included progression-free survival (PFS). As previously reported,⁴ patients who received ivosidenib achieved a 63% reduced risk of disease progression (HR, 0.37; 95% CI 0.25-0.54; one-sided P <.0001).

The key secondary end point was OS, but additional secondary outcomes also included objective response rate (ORR), safety tolerability, and QOL. Investigators assessed HRQoL via the EORTC QLQ-C30 and the EORTC QLQ-BIL21. HRQOL was assessed on the first day of treatment, every 4 weeks throughout treatment, and every 12 weeks following treatment.

“The ClarIDHy study showed that patients with advanced IDH1-mutated cholangiocarcinoma were likely to maintain their HRQoL over the duration of treatment,” Chamberlain concluded. “For some patients, the duration of treatment and preservation of HRQOL was over 1 year.”

References

1. 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. J Clin Oncol. 2022;40(suppl; abstr 388). doi:10.1200/JCO.2022.40.4_suppl.012
2. Servier announces FDA approval of TIBSOVO (ivosidenib tablets) in IDH1-mutated cholangiocarcinoma. Cision. News release. Accessed August 25, 2021. https://prn.to/3uDRLzR
3. Zhu AX, Macarulla T, Javle MM, et al. Final overall survival efficacy results of ivosidenib for patients with advanced cholangiocarcinoma with IDH1 mutation: the phase 3 randomized clinical ClarIDHy trial. JAMA Oncol. Published online September 23, 2021. doi:10.1001/jamaoncol.2021.3836
4. Abou-Alfa GK, Macarulla T, Javle MM, et al. Ivosidenib in IDH1-mutant, chemotherapy-refractory cholangiocarcinoma (ClarIDHy): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study [published correction appears in Lancet Oncol. 2020 Oct;21(10):e462]. Lancet Oncol. 2020;21(6):796-807. doi:10.1016/S1470-2045(20)30157-1.