OS09.4.A EARLY TUMOR VOLUME CHANGES PREDICT CLINICAL OUTCOMES IN MIDH1/2 GLIOMA: POST-HOC RESULTS FROM THE PHASE 3 INDIGO TRIAL

Abstract BACKGROUND In the Phase 3 INDIGO trial (NCT04164901), vorasidenib, an oral, brain-penetrant, dual inhibitor of mutated isocitrate dehydrogenase 1/2 (mIDH1/2), improved progression-free survival (PFS) versus placebo in patients with mIDH1/2 diffuse glioma. While two-dimensional (2D) measurements of tumors remain the standard for clinical trials, tumor volume better captures the true extent of disease and can provide quantitative evaluation of treatment effect through analysis of growth dynamics. We utilized data from the INDIGO trial to evaluate tumor volume as a predictive marker in mIDH1/2 glioma. MATERIAL AND METHODS PFS was assessed by blinded independent review committee (BIRC) using modified Response Assessment in Neuro-Oncology for low-grade gliomas criteria (2D). Tumor volume was measured using semiautomated segmentation on magnetic resonance imaging scans at baseline and every 12 weeks (3D). Pearson correlation coefficient and mixed-effect models were used to evaluate relationships between 2D and 3D assessments. Cox proportional hazards models were used to analyze associations between baseline tumor volume, tumor growth rate and clinical outcomes, including PFS and time to next intervention (TTNI). RESULTS Despite more fluctuations and variability in 2D measurements than in 3D measurements over time, there was a strong positive correlation both for individual measurements (R=0.858) and when accounting for repeated measurements within the same patients (R=0.861). While baseline tumor volume appeared prognostic for TTNI, it only trended toward association with PFS by BIRC. Increase in volumetric growth at any time point during treatment increased the risk of progression or death (hazard ratio [HR] 1.061; 95% confidence interval [CI] 1.038, 1.084; P<0.0001) and the risk of next intervention or death (HR 1.059; 95% CI 1.037, 1.082; P<0.0001). Volumetric growth during the first 6 months of treatment was predictive of PFS (HR 1.046; 95% CI 1.026, 1.067; P<0.0001) and TTNI (HR 1.051; 95% CI 1.031, 1.071; P<0.0001) regardless of treatment assignment. CONCLUSION Using data from the Phase 3 INDIGO trial of patients with mIDH1/2 glioma, we found a high correlation between 2D and 3D assessments. While baseline tumor volume showed variable prognostic value, the substantial association between volumetric growth rate and outcomes suggests that early tumor volume changes can serve as reliable surrogate for both PFS and TTNI. These findings support the inclusion of 3D volumetric assessment in future clinical trials and treatment evaluation of diffuse gliomas. Study sponsored by Servier.

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Journal
Neuro-Oncology
Published
2025-10-01
DOI
https://doi.org/10.1093/neuonc/noaf193.070
Primary Topic
Glioma Diagnosis and Treatment
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article
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article

OS09.4.A EARLY TUMOR VOLUME CHANGES PREDICT CLINICAL OUTCOMES IN MIDH1/2 GLIOMA: POST-HOC RESULTS FROM THE PHASE 3 INDIGO TRIAL

Andreas Felix Hottinger, Shlomit Yust‐Katz, Warren Mason, John Clarke et al.
Neuro-Oncology
Glioma Diagnosis and Treatment
article

OS09.4.A EARLY TUMOR VOLUME CHANGES PREDICT CLINICAL OUTCOMES IN MIDH1/2 GLIOMA: POST-HOC RESULTS FROM THE PHASE 3 INDIGO TRIAL

Andreas Felix Hottinger, Shlomit Yust‐Katz, Warren Mason, John Clarke, Martin J. van den Bent, Islam Hassan, Pierre Giglio, Ingo K. Mellinghoff, Patrick Y. Wen, Benjamin M. Ellingson, Deborah T. Blumenthal, Yoshie Umemura, Liam Welsh, François Ducray, Yoshiki Arakawa, M. de la Fuente, Jennifer C. Perry, Elizabeth A. Maher, Timothy F. Cloughesy, Mehdi Touat, Katherine B. Peters, Burt Nabors, Juan Manuel Sepúlveda-Sánchez, Wolfgang Wick, Susan Pandya, Matthias Holdhoff, Dongdong Zhao, Riccardo Soffietti, Jose Carlos Méndez, Linda S. Steelman
article en

Abstract

Abstract BACKGROUND In the Phase 3 INDIGO trial (NCT04164901), vorasidenib, an oral, brain-penetrant, dual inhibitor of mutated isocitrate dehydrogenase 1/2 (mIDH1/2), improved progression-free survival (PFS) versus placebo in patients with mIDH1/2 diffuse glioma. While two-dimensional (2D) measurements of tumors remain the standard for clinical trials, tumor volume better captures the true extent of disease and can provide quantitative evaluation of treatment effect through analysis of growth dynamics. We utilized data from the INDIGO trial to evaluate tumor volume as a predictive marker in mIDH1/2 glioma. MATERIAL AND METHODS PFS was assessed by blinded independent review committee (BIRC) using modified Response Assessment in Neuro-Oncology for low-grade gliomas criteria (2D). Tumor volume was measured using semiautomated segmentation on magnetic resonance imaging scans at baseline and every 12 weeks (3D). Pearson correlation coefficient and mixed-effect models were used to evaluate relationships between 2D and 3D assessments. Cox proportional hazards models were used to analyze associations between baseline tumor volume, tumor growth rate and clinical outcomes, including PFS and time to next intervention (TTNI). RESULTS Despite more fluctuations and variability in 2D measurements than in 3D measurements over time, there was a strong positive correlation both for individual measurements (R=0.858) and when accounting for repeated measurements within the same patients (R=0.861). While baseline tumor volume appeared prognostic for TTNI, it only trended toward association with PFS by BIRC. Increase in volumetric growth at any time point during treatment increased the risk of progression or death (hazard ratio [HR] 1.061; 95% confidence interval [CI] 1.038, 1.084; P<0.0001) and the risk of next intervention or death (HR 1.059; 95% CI 1.037, 1.082; P<0.0001). Volumetric growth during the first 6 months of treatment was predictive of PFS (HR 1.046; 95% CI 1.026, 1.067; P<0.0001) and TTNI (HR 1.051; 95% CI 1.031, 1.071; P<0.0001) regardless of treatment assignment. CONCLUSION Using data from the Phase 3 INDIGO trial of patients with mIDH1/2 glioma, we found a high correlation between 2D and 3D assessments. While baseline tumor volume showed variable prognostic value, the substantial association between volumetric growth rate and outcomes suggests that early tumor volume changes can serve as reliable surrogate for both PFS and TTNI. These findings support the inclusion of 3D volumetric assessment in future clinical trials and treatment evaluation of diffuse gliomas. Study sponsored by Servier.

Neuro-OncologyVol. 27(Supplement_3)
Sunnybrook Health Science Centre (CA), Barrow Neurological Institute (US), Memorial Sloan Kettering Cancer Center (US), University of California, Los Angeles (US), Tel Aviv University (IL), German Cancer Research Center (DE), University of California, San Francisco (US), University of Toronto (CA), Kyoto University (JP), University of Utah (US), Heidelberg University (DE), Rabin Medical Center (IL), Huntsman Cancer Institute (US), Toronto General Hospital (CA), Erasmus MC (NL), University Hospital Heidelberg (DE), Centre Hospitalier Universitaire Vaudois (CH), Health Sciences Centre (CA), The Ohio State University Wexner Medical Center (US), University of Alabama at Birmingham (US), Sorbonne Université (FR), Assistance Publique – Hôpitaux de Paris (FR), Hospices Civils de Lyon (FR), Hospital Universitario 12 De Octubre (ES), Hôpital Pierre Wertheimer (FR), Michigan Medicine (US), Dana-Farber Cancer Institute (US), Michigan Center for Translational Pathology (US), Royal Marsden Hospital (GB), Pitié-Salpêtrière Hospital (FR), Centre de Recherche en Cancérologie de Lyon (FR), Duke Medical Center (US), Sylvester Comprehensive Cancer Center (US), Sidney Kimmel Comprehensive Cancer Center (US), University of Turin (IT), The University of Texas Southwestern Medical Center (US), Erasmus University Rotterdam (NL)
Openalex Percentile: Top 62%
Glioma Diagnosis and Treatment
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