Key points are not available for this paper at this time.
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 m IDH cancers, including acute myeloid leukaemia (AML), cholangiocarcinoma (CCA), glioma and conventional chondrosarcoma. In the phase 3 clinical trial ClarIDHy, patients with m IDH1 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 m IDH1 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 m IDH1 chondrosarcoma. The phase 3 clinical trial INDIGO explored the use of vorasidenib for the treatment of Central Nervous System World Health Organization grade 2 m IDH 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 m IDH cancers.
Bridgewater et al. (Sun,) studied this question.