Adult Brain Tumors Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Management of Specific Tumor Types and Locations
In summary, there was no survival advantage for the use of dose-dense temozolomide versus standard-dose temozolomide in newly diagnosed glioblastoma patients, regardless of MGMT status. The efficacy of dose-dense temozolomide for patients who have recurrent glioblastoma, however, is yet to be determined.
Bevacizumab in newly diagnosed glioblastoma
In 2013, final data from two multicenter, phase III, randomized, double-blind, placebo-controlled trials of bevacizumab in patients who have newly diagnosed glioblastoma were reported: RTOG 0825 (NCT00884741) and the Roche-sponsored AVAglio (NCT00943826).[7,8][Level of evidence: 1iA] Patients in both studies were randomly assigned to receive standard therapy (chemoradiation with temozolomide) or standard therapy plus bevacizumab. OS and PFS were coprimary endpoints in both trials, and these outcomes were similar. Bevacizumab did not improve OS in either study (median OS was 16–17 months for each arm in both studies); however, it increased median PFS to a similar degree (AVAglio study: 10.6 vs. 6.2 months; HR, 0.64; P < .0001; RTOG 0825 study: 10.7 vs. 7.3 months; HR, 0.79; P = .007). The PFS result in the AVAglio study was statistically significant and associated with clinical benefit because bevacizumab-treated patients remained functionally independent for longer (9.0 months vs. 6.0 months) and went longer before their Karnofsky Performance scale deteriorated (HR, 0.65; P < .0001). Furthermore, bevacizumab-treated patients went longer before corticosteroids were initiated (12.3 vs. 3.7 months; HR, 0.71; P = .002), and a larger proportion of patients was able to discontinue corticosteroids if they were already taking them (66% vs. 47%). However, the PFS result in the RTOG 0825 trial did not meet the prespecified significance level (P = .004). Of note, there was significant crossover in both trials (approximately 40% of RTOG 0825 patients and approximately 30% of AVAglio patients received bevacizumab at the first sign of disease progression).
The two trials had contradictory results in health-related quality of life (HRQoL) and neurocognitive outcomes studies. In the mandatory HRQoL studies in the AVAglio trial, bevacizumab-treated patients experienced improved HRQoL, but bevacizumab-treated patients in the elective RTOG 0825 studies showed more decline in patient-reported HRQoL and neurocognitive function. The reasons for these discrepancies are unclear.