Abstract
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.