Abstract
INTRODUCTION: The INDIGO study (NCT04164901) showed that vorasidenib, an oral, brain-penetrant, dual inhibitor of mutant isocitrate dehydrogenase (mIDH) 1/2, significantly improved imaging-based progression-free survival and time-to-next-intervention compared with placebo in patients with grade 2 mIDH1/2 glioma previously treated with surgery only. Given the limitations of traditional bi-dimensional measurements, evaluating volumetry and tumor growth rate (TGR) is an additional method of measuring treatment effect in these diffuse growing tumors. METHODS: Magnetic resonance imaging (MRI) scans were performed at baseline and every 12 weeks on-treatment; up to three pre-treatment MRI scans were requested when available. Tumor volumes were derived per blinded independent review committee using a semi-automated approach. TGR was defined as percentage change in tumor volume every 6 months. Patients with evaluable baseline and ≥ 1 MRI during the corresponding period were included in the analysis. The difference in TGR in each arm was assessed by slope of tumor growth over time using a linear mixed model. RESULTS: 331 patients were randomized to vorasidenib (n=168) or placebo (n=163). Median follow-up was 14.2 months. On-treatment TGR was −2.5% (95% CI, −4.7, −0.2) with vorasidenib (n=167) and 13.9% (95% CI, 11.1, 16.8) with placebo (n=161). In patients with available imaging data, TGR pre- and post-treatment with vorasidenib (n=56) was 13.2% (95% CI, 10.3, 16.3) and −3.3% (95% CI, −5.2, −1.2), respectively, while placebo (n=67) was 18.3% (95% CI, 15.0, 21.7) and 12.2% (95% CI, 9.5, 14.9), respectively. In patients who crossed over from placebo with available imaging data (n=38), TGR pre- and post-crossover was 22.4% (95% CI, 15.7, 29.4) and 5.2% (95% CI, −3.8, 15.0), respectively. CONCLUSIONS: Tumor growth was observed in patients with mIDH1/2 gliomas before receiving vorasidenib or placebo. Treatment with vorasidenib reduced the TGR and shrunk tumor volume, whereas continued growth in tumor volume was observed in patients receiving placebo.