RTOG 0525 Subanalysis Finds Worse Outcomes With Dose-Dense vs Standard Adjuvant Temozolomide in Glioblastoma
A phase III trial (Radiation Therapy Oncology Group [RTOG] 0525; N = 833) comparing dose-dense vs standard-dose temozolomide maintenance in newly diagnosed glioblastoma showed no differences in overall survival or progression-free survival between treatments. A substudy of the trial, reported in the Journal of Clinical Oncology by Terri S. Armstrong, PhD, of The University of Texas MD Anderson Cancer Center, and colleagues, assessed net clinical benefit of the treatments in a subpopulation of patients. They found that patients in the dose-dense group exhibited greater symptom burden and functional interference and decreased global health and motor function. Baseline measures and early changes predictive of overall survival and progression-free survival were identified.
Study Details
The substudy was performed in 182 patients, including 92 in the standard-dose group and 90 in the dose-dense group. Net clinical benefit was assessed by tests of neurocognitive function (Hopkins Verbal Learning Test–Revised [HVLT-R], Trail Making Test [TMT], and Controlled Oral Word Association [COWA]), symptoms (MD Anderson Symptom Inventory–Brain Tumor module [MDASI-BT]), and quality of life (European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]–C30/BN20).
Patient characteristics were generally balanced between the standard-dose and dose-dense groups; median age was 57 vs 59 years, 58% vs 46% were male, 68.5% vs 72 % had Karnofsky performance status of 90 to 100, 65% vs 61% had total resection, 56.5% and 58% had unmethylated MGMT, and 63% vs 64% were recursive partitioning analysis class IV.
Worse Outcome in Dose-Dense Group
There was greater deterioration in the dose-dense group from baseline to treatment cycle 4 in the global health (P = .03) and motor function (P = .014) subscales of the EORTC QLQ-C30/BN20 and in overall symptom burden (P = .03), overall symptom interference (P = .03), activity-related (P = .02), and work and walking (P = .01) symptom interference subscales of the MDASI-BT. There were no differences between groups in measures of neurocognitive function.
Factors Predicting Survival
Baseline measures (continuous) significantly predictive of overall survival on multivariate analysis were the physical functioning scale (hazard ratio [HR] = 0.99, P = .029) and nausea/vomiting item (HR = 1.02, P = .030) of the EORTC QLQ-C30/BN20, delayed recognition on the HVLT-R (HR = 0.87, P = .022), and COWA (HR = 0.81, P = 0.10).
Change from baseline to cycle 1 was significantly predictive of overall survival for cognitive function (HR = 1.95, P = .004), motor dysfunction item (HR = 1.59, P = .041), and hair loss item (HR = 0.57, P = .039) on the EORTC QLQ-C30/BN20, cognitive factor on the MDASI-BT (HR = 1.82, P = .012), total recall on the HVLT-R (HR = 1.90, P = .013), and part B of the TMT (HR = 2.11, P = .003).
Baseline measures significantly predictive of progression-free survival were the physical functioning scale and the constipation item on the EORTC QLQ-C30/BN20 and COWA. Early changes significantly predictive of progression-free survival were those on the motor dysfunction item of the EORTC QLQ-C30/BN20, neurologic factor on the MDASI-BT, and delayed recall on the HVLT-R.
The investigators concluded: “Longitudinal collection of [net clinical benefit] measures is feasible in cooperative group studies and provides an added dimension to standard outcome measures. Greater adverse symptom burden and functional interference, as well as decreased global health and motor function were observed in patients randomly assigned to the dose-dense arm. Baseline and early change in net clinical benefit measures were associated with decreased rates of survival.”
Dr. Armstrong and Jeffrey S. Wefel, PhD, ABPP, of The University of Texas MD Anderson Cancer Center, contributed equally to the work.
The study was supported by National Cancer Institute grants and by Merck Pharmaceuticals.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
