Vorasidenib successfully targets IDH1/2-mutated glioma

Results from the global, randomised, double-blinded, phase 3 INDIGO study showed that vorasidenib significantly improved progression-free survival (PFS) in patients with IDH1/2-mutated glioma who had prior surgery only.

Isocitrate dehydrogenase (IDH)-mutant grade 2 gliomas are malignant brain tumours that cause considerable disability and premature death. Currently, no curative therapy is available. Vorasidenib is an oral brain-penetrant inhibitor of mutant IDH1 and IDH2 enzymes that previously showed activity in IDH-mutant gliomas [1]. Dr Ingo Mellinghoff (Memorial Sloan Kettering Cancer Center, NY, USA) presented the randomised phase 3 trial INDIGO trial (NCT04164901), which evaluated the efficacy of vorasidenib [2,3].

INDIGO enrolled 331 participants with IDH-mutated, grade 2 gliomas who had prior surgery only and who did not need immediate chemotherapy or radiotherapy. Participants were randomised 1:1 to receive vorasidenib or placebo. Cross-over to vorasidenib after progression was allowed for patients in the placebo arm. The primary endpoint was (imaging-based) PFS. A key secondary endpoint was time from randomisation to the initiation of first subsequent anti-cancer therapy or death because of any cause (TTNI).

Median PFS was 27.7 months for patients treated with vorasidenib compared with 11.1 months for patients treated with placebo (HR 0.39; P< 0.0001). Median TTNI was not reached for patients treated with vorasidenib compared with 17.8 months for participants treated with placebo (HR 0.26; P<0.0001). The probability of not receiving subsequent anti-cancer therapy at 24 months was 83.4% in the vorasidenib arm compared with 27.0% in the placebo arm.

Treatment-related adverse events grade ≥3 were more common in the vorasidenib arm compared with placebo: 22.8% versus 13.5%, respectively. Treatment interruption due to treatment-related adverse events was observed in 29.9% and 22.7% of participants, respectively; discontinuation of treatment was observed in 3.6% and 1.2% of participants, respectively.

“The results of the INDIGO trial prove the effectiveness of targeting mutant IDH1/2 in low-grade gliomas and has the potential to shift the treatment landscape in this disease,” Dr Mellinghoff concluded.

1. Mellinghoff IK, et al. Nat Medicine. 2023;29:6150622.
2. Mellinghoff IK, et al. INDIGO: A global, randomized, double-blinded, phase 3 study of vorasidenib versus placebo in patients with residual or recurrent grade 2 glioma with an IDH1/2 mutation. Abstract LBA1, ASCO Annual Meeting 2023, 2–6 June, Chicago, USA.
3. Mellinghoff IK, et al. N Engl J Med 2023;June 4. DOI: 10.1056/NEJMoa2304194.

 

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Posted on 1 August, 20231 August, 2023