A recent, updated predictive analysis of the three World Health Organization (WHO)-defined molecular subgroups based on IDH mutation status and 1p/19q codeletion status represented in the high-risk treatment arms of a phase III trial found that both IDH-mutant subgroups may derive benefit from the addition of PCV (procarbazine, lomustine, and vincristine) chemotherapy to radiotherapy. These data were presented by Bell et al at the 2019 ASCO Annual Meeting (Abstract 2002).
NRG-RTOG 9802 was a phase III trial that assessed patients with high-risk low-grade gliomas (defined as patients at least 40 years old or who have had incomplete tumor removal) that were treated with radiotherapy with or without PCV chemotherapy after the patients received a biopsy or surgical resection. This analysis studied a subset of the specimens from which tissue was available for molecular profiling.
“This is the first phase III trial to evaluate the predictive value of WHO subgroups in low-grade gliomas using long-term overall survival data with the current standard of care. The results support the notions that there are benefits of PCV therapy to RT for both IDH-mutated, 1p/19q noncodeleted and IDH-mutated, 1p/19q codeleted subgroups; whereas, high-risk low-grade glioma patients with IDH wild-type tumors did not demonstrate any benefit from this treatment,” stated first author Erica H. Bell, PhD, Associate Professor of the Department of Radiation Oncology at The Ohio State University.
One hundred and six specimens of the 251 eligible patients from the trial could be analyzed as they had sufficient tissue and quality DNA for profiling. Of these specimens, 41% were categorized as IDH-mutated, 1p/19q noncodeleted, 35% were IDH-mutated, 1p/19q codeleted, and 24% were IDH wild-type. No statistically significant differences between progression-free survival (PFS) and overall survival (OS) was observed with the addition of PCV chemotherapy in the IDH wild-type subgroup; however, both IDH-mutant subgroups were significantly correlated with longer PFS (IDH-mutated, 1p/19q noncodeleted, P = .003; IDH-mutated, 1p/19q codeleted, P < .001) and OS (IDH-mutated, 1p/19q noncodeleted, P = .013; IDH-mutated, 1p/19q codeleted, P = .029) in the radiotherapy plus PCV chemotherapy arm.
“This study demonstrates the importance of incorporating the new WHO subgroups into the clinical routine, as it enhances the prognostic and now predictive clarification of patients with low-grade glioma, provides further insight into resistance to radiation and PCV [chemotherapy], and guides clinical decision-making,” stated senior author Arnab Chakravarti, MD, Chair of Radiation Oncology at The Ohio State University Comprehensive Cancer Center–Arthur G. James Cancer Hospital.
Disclosure: This project was supported by The National Cancer Institute grants, Brain Tumor Funders Collaborative Grant, and The Ohio State University CCC. For full disclosures of the study authors, visit coi.asco.org.
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