In a post hoc analysis from the phase III NRG Oncology/RTOG 9802 trial reported in the Journal of Clinical Oncology, Bell et al found that postradiation chemotherapy was associated with a better outcome vs radiotherapy alone in patients with IDH-mutant, high-risk, low-grade glioma, irrespective of 1p/19q codeletion status.
As stated by the investigators, “NRG Oncology/RTOG 9802 is a practice-changing study for patients with World Health Organization (WHO) low-grade glioma (grade II), as it was the first to demonstrate a survival benefit of adjuvant chemoradiotherapy over radiotherapy. This post hoc study sought to determine the prognostic and predictive impact of the WHO-defined molecular subgroups and corresponding molecular alterations within NRG Oncology/RTOG 9802.”
Study Details
The study assessed the effect on outcomes of WHO-defined molecular subgroups including IDH1/2 mutation and 1p/19q codeletion status in patients receiving adjuvant postradiation chemotherapy with procarbazine, lomustine, and vincristine vs radiotherapy alone.
“Importantly, this post hoc analysis supports the notion that patients with IDH-mutant, high-risk, low-grade glioma regardless of codeletion status receive benefit from the addition of procarbazine, lomustine, and vincristine.”— Bell et al
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Key Findings
Median follow-up among all patients in the trial was 9.0 years. Of 251 eligible patients, 106 had molecular subgroup data available for analysis. Of these, 26 (24%) were IDH wild-type, 43 (41%) were IDH-mutant/noncodeleted, and 37 (35%) were IDH-mutant/codeleted.
Receipt of postradiation chemotherapy was associated with improved progression-free survival vs radiotherapy in both the IDH-mutant/noncodeleted group (median = 10.4 vs 3.3 years, hazard ratio [HR] = 0.32, P = .003) and in the IDH-mutant/codeleted group (median = not reached vs 5.8 years, HR = 0.13, P < .001).
Postradiation chemotherapy was also associated with improved overall survival in both the IDH-mutant/noncodeleted group (median = 11.4 vs 4.3 years, HR = 0.38, P = .013) and in the IDH-mutant/codeleted group (median = not reached vs 13.9 years, HR = 0.21, P = .029).
No significant difference in progression-free or overall survival was observed with the addition of postradiation chemotherapy in the IDH wild-type group.
The investigators concluded, “This study is the first to report the predictive value of the WHO-defined diagnostic classification in a set of uniformly treated patients with low-grade glioma in a clinical trial. Importantly, this post hoc analysis supports the notion that patients with IDH-mutant, high-risk, low-grade glioma regardless of codeletion status receive benefit from the addition of procarbazine, lomustine, and vincristine.”
Arnab Chakravarti, MD, of The Ohio State University Comprehensive Cancer Center, The Ohio State University Medical School, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by grants from the National Cancer Institute. For full disclosures of the study authors, visit ascopubs.org.
