Comparative impact of treatment on patient reported outcomes (PROs) in patients with glioblastoma (GBM) enrolled in RTOG 0825.

Abstract

2003 Background: RTOG 0825 tested if adding bevicizumab (BEV) to standard chemoradiation improves survival (OS) or progression free survival (PFS) in newly diagnosed GBM. While OS was equivalent, PFS was longer with Bev (Arm 2) than with placebo (Arm 1). Patients completed quality of life and symptom PROs to evaluate clinical benefit. Methods: The M.D. Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) and the EORTC core Quality of life Questionnaire and brain tumor module (EORTC QLQ-C30/BN20), were completed by pts at baseline (B) and longitudinally (wk 6, 10, 22, 34, and 46) while on study. The difference between treatment arms were compared from B with evaluation in subsequent weeks in those pts without disease progression; and early change (EC) (baseline to wk 10) between those with and without progression as predictors for OS and PFS. Results: 542pts consented to participate on this trial, and 507 randomized pts participated, with completion of forms by 94% at baseline, 75% at wk 10, 61% at wk 22, and 58% at wk 34. There was a trend for all MDASI-BT symptom groupings to be worse in Arm 2, with significant findings in treatment symptoms at wk 22 and wk 34; both affective and generalized disease symptoms were also significantly worse. For EORTCQLQ30/BN20, differential effects varied at each time point, with no persistent differences. For the MDASI-BT, B neurologic symptom grouping and EC in cognitive symptoms were prognostic for both OS and PFS. For the EORTC QLQ30/BN20, global QOL and motor dysfunction at B as well as EC in communication and leg weakness were prognostic for OS; whereas physical function at B and EC in headaches, seizures, and weak legs were prognostic for PFS. Conclusions: The longitudinal collection of PROs in this phase III trial revealed important treatment-related differences as there was overall more deterioration in symptoms and QOL in Arm 2 as compared to Arm 1, with persistent significant differences in treatment associated symptoms. B and EC tumor associated symptoms on both PRO tools were prognostic for OS and PFS. Longitudinal modeling is ongoing to further assess for differential impact of treatment on symptoms and QOL. Support: U10 CA21661, U10 CA37422 and Genentech, Inc. Clinical trial information: NCT00884741.