European Journal of Cancer, Supplement · Published 2026-03-01 · DOI 10.1016/j.ejcsup.2025.12.001
The use of mutant isocitrate dehydrogenase (mIDH) inhibitors has been investigated and has shown significant improvement in survival outcomes in patients with a range of mIDH cancers, including acute myeloid leukaemia (AML), cholangiocarcinoma (CCA), glioma and conventional chondrosarcoma. In the phase 3 clinical trial ClarIDHy, patients with mIDH1 CCA treated with ivosidenib had improved overall survival (OS) compared to those treated with placebo (hazard ratio [HR]: 0.79 [95% confidence interval [CI]: 0.56–1.12]; P=0.09). In the phase 3 AGILE study, patients with mIDH1 AML treated with ivosidenib plus azacitidine showed improved OS compared to those treated with placebo plus azacitidine (HR: 0.42 [95% CI: 0.27–0.73]; P=0.001). In conventional chondrosarcoma, ivosidenib demonstrated efficacy in a phase 1 trial and the ongoing phase 3, placebo-controlled clinical trial CHONQUER will investigate the use of ivosidenib in patients with unresectable, progressive, conventional mIDH1 chondrosarcoma. The phase 3 clinical trial INDIGO explored the use of vorasidenib for the treatment of Central Nervous System World Health Organization grade 2 mIDH glioma and showed that vorasidenib had a progression-free survival benefit over placebo in previously untreated patients (HR: 0.39 [95% CI: 0.27–0.56]; P<0.0001). Across these studies, mIDH inhibitors were well-tolerated. Current efforts focus on further evaluating the efficacy and safety of mIDH inhibitors in different lines of therapy, in combination with other anti-neoplastic agents, and in other mIDH cancers.
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