Time to deterioration in dimensions of health-related quality of life (HRQL) for patients with recurrent glioblastoma multiforme (GBM): Results from the randomized, phase III trial of enzastaurin (ENZ) versus lomustine (CCNU)

Abstract

2040 Background: One goal of therapy for recurrent GBM is to delay worsening in HRQL, with interventions expected to have greatest impact on physical and functional domains. HRQL assessment in recurrent GBM has been limited by deterioration of patient (pt) status. We report HRQL results from a multinational phase III trial. Methods: Pts with recurrent GBM were randomized 2:1 to ENZ 500 mg daily or CCNU 100–130 mg/m2 every 6 weeks. Pts and proxies completed the 50-item Functional Assessment of Cancer Therapy - Brain (FACT-Br) (version 4) prior to randomization, approximately every 3 weeks while on therapy and then 30 days after discontinuation. Time to deterioration (TtD) for each pt was defined as an 11-point decrease in the 148-point Trial Outcome Index (TOI; physical and functional well-being plus brain tumor-specific concerns) or death. Only pts with baseline FACT-Br data were included in the analysis. Proxy data were used when pts were unable to complete the FACT-Br and if there were sufficient dyad data to establish an imputation pattern. TtD was analyzed using Kaplan-Meier methods. To assess differences between arms in TOI subscales, change from baseline was analyzed with a mixed-effects analysis of variance model. Results: Enrollment was terminated after an interim analysis. Of 266 randomized pts, 159 / 174 (91%) ENZ and 82 / 92 (89%) CCNU pts were analyzed for TtD. Baseline scores for TOI were not statistically different between arms (p=0.638). Pt compliance for completing the FACT-Br on-study over the first 6 months was 77% for ENZ and 78% for CCNU; use of proxy data increased compliance to 79% and 81%, respectively. Median TtD was 2.27 months for ENZ and 2.33 months for CCNU with 6-month rates of 18% and 29%, respectively (hazard ratio = 1.12 [95% CI: 0.77–1.63]; log-rank p-value = 0.54; 47% censoring). There were no differences between arms in change from baseline in physical and functional well-being or in brain tumor-specific concerns (p>0.05). Conclusions: Assessment of HRQL is feasible in pts with recurrent GBM. No difference in time that physical and functional domains of HRQL were maintained was detected between ENZ and CCNU. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Eli Lilly Eli Lilly, MGI Pharma, Pfizer Oncology, Schering-Plough Eli Lilly Eli Lilly, Merck, Pfizer Oncology, Schering-Plough Eli Lilly Schering-Plough