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Addition of bevacizumab to temozolomide, radiation improved outcomes in glioblastoma
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CHICAGO — The addition of bevacizumab to a regimen of temozolomide and radiotherapy improved PFS by nearly 3 months in a cohort of patients with glioblastoma, according to study results presented at the ASCO Annual Meeting.
The randomized, double-blind, placebo-controlled trial included 921 patients aged at least 18 years with newly diagnosed disease. Researchers assigned 458 patients to bevacizumab (Avastin, Genentech) and 463 patients to placebo.
Researchers evaluated the addition of bevacizumab or placebo 10 mg/kg every other week to a 6-week regimen of temozolomide 75mg/m2/d plus radiation 2Gy, five days a week. This regimen was then followed by 28 days without treatment, six cycles of temozolomide 150 to 200 mg/m2 per day for 5 days every 4 weeks, with bevacizumab or placebo 10 mg/kg every 2 weeks. Patients then received single-agent bevacizumab or placebo 15 mg/kg every 3 weeks until disease progression or unacceptable toxicity.
Investigator-assessed PFS and OS served as co-primary endpoints. Health-related quality of life — defined as EORTC QLQ-C30 and BN20, with five prespecified domains based on relevance in glioblastoma — served as the secondary endpoint. Health-related quality of life time to definitive deterioration was defined “as time from randomization to ≥10 point deterioration from baseline with no subsequent improvement, progressive disease or death,” according to the researchers.
Karnofsky Performance Status and corticosteroid use were evaluated in an exploratory analysis.
Patient baseline characteristics were balanced.
Researchers reported bevacizumab was associated with a significant improvement in PFS (HR=0.64; 95% CI, 0.55–0.74). The median PFS was 10.6 months in the study drug group and 6.2 months in the placebo group. Patients who received bevacizumab also demonstrated delayed time to definitive deterioration in quality of life compared with those in the placebo arm (P<.0001).
Patients in both the bevacizumab and placebo arms maintained functional independence, defined as Karnofsky Performance Status ≥ 70%, during PFS (median 9 months in the bevacizumab arm vs. 6 months in the placebo arm).
A subset of patients was receiving ≥ 2mg corticosteroids at baseline. Among this group, discontinuation (≥ 5 consecutive days) occurred at 66% in the bevacizumab arm and 47% in the placebo arm.
Among patients defined as off corticosteroids at baseline (less than 2 mg), the time to initiation of corticosteroids was significantly longer with bevacizumab than placebo (12.3 months vs. 3.7 months; HR=0.71; 95% CI 0.57–0.88).
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Henriksson R. #2005. Presented at: ASCO Annual Meeting; May 31-June 4, 2013; Chicago.
Disclosure: The researchers report research funding and honoraria from, as well as employment relationships and consultant/advisory roles with, Apogenics, AstraZeneca, Boehringer Ingelheim, Celgene, Genentech, Lilly, Merck Serono, MSD, NewGen Therapeutics, Roche and Tocagen.
Perspective
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Joseph R. Bertino, MD
In both this study and the study by Gilbert and colleagues (Abstract #1), bevacizumab showed an increase in PFS. Survival data are not presented in this study. The reasons for the lack of impact of bevacizumab on survival — despite a significant improvement in PFS when this agent is added to chemoradiation — are not clear. OS results from this study will be important.
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