• Oncology Clinical Trials
• Head & Neck Cancers

• Oncology
• Oncology Clinical Trials
• Head & Neck Cancers

Data from a Phase 3 study indicate that the use of bevacizumab (BEV) in glioblastoma should not be extended to the first-line setting. Currently, BEV is approved by the United States Food and Drug Administration for the treatment of recurrent glioblastoma.

Findings from the double-blind, placebo-controlled, randomized trial entitled Temozolomide and Radiation Therapy With or Without Bevacizumab in Treating Patients With Newly Diagnosed Glioblastoma [RTOG 0825; NCT00884741; Gilbert MR et al. J Clin Oncol 2013 (suppl; abstr 1)] were announced by Mark R. Gilbert, MD, University of Texas MD Anderson Cancer Center, Houston, Texas, USA, on behalf of the participating cooperative groups: RTOG, NCCTG and ECOG.

The current standard of care for glioblastoma is surgical resection followed by chemoradiation with temozolomide (TMZ), but despite this treatment average survival remains <18 months. Angiogenesis is a hallmark feature of glioblastoma, and vascular endothelial growth factor (VEGF)-A is the most common angiogenic factor produced by glioblastoma tumors. Dr. Gilbert and colleagues therefore explored the utility of BEV, a humanized monoclonal antibody against VEGF-A with demonstrated activity in recurrent glioblastoma, as first-line therapy.

In the trial, 637 neurologically stable adults with newly diagnosed glioblastoma underwent 3 weeks of standard chemoradiation with daily TMZ. Patients were then randomized to complete chemoradiation with TMZ with either either placebo or BEV (10 mg/kg IV Q2W). Patients then continued with maintenance TMZ (Days 1 to 5 of a 28-day cycle) with either placebo or BEV Q2W through 6 to 12 cycles. All patients had undergone surgical resection before starting chemoradiation; ∼60% in each arm had gross total resection. Nearly 80% of patients received intensity-modulated radiation therapy. At disease progression, the study treatment arm designation could be revealed, at which time patients were allowed to cross over or continue BEV. In the placebo arm, 40.7% of patients crossed over to BEV; 20.9% of patients in the BEV arm stayed on BEV after progression (Table 1). The coprimary endpoints were overall survival (OS) and progression-free survival (PFS).

Adverse events that were more common with BEV compared with placebo included hypertension (4.6% vs 1.0%), deep vein thrombosis/pulmonary embolism (9.9% vs 7.7%), wound healing issues (2.3.% vs 1.0%), gastrointestinal perforation (1.3% vs 0.7%), significant hemorrhage (1.3% vs 1.0%), and neutropenia (15.1% vs 7.3%).

Some 40.7% of pateints in the placebo arm crossed over to BEV; 20.9% of patients in the BEV arm sayted on BEV after progression (Table 1).

The median OS was 16.1 months in those randomized to placebo versus 15.7 months with randomization to BEV (HR, 1.13; p=0.21). The median PFS was longer by 3.4 months in the BEV group relative to the placebo group (10.7 vs 7.3 months; HR, 0.79; p=0.007), but this difference did not reach the prespecified 30% reduction in hazard of failure with a p value of 0.004 prescribed for the study. Methylation status of the O-6 Methylguanine-DNA Methyltransferase (MGMT) gene promoter was prognostic, with unmethylated status demonstrating significantly worse median OS and PFS. A subgroup analysis based on MGMT methylation status, a 9-gene expression signature, and Clinical Prognostic Groups found no differences in outcomes between treatments by subgroup (Table 2).

A prespecified analysis evaluated symptom burden, health-related quality of life and neurocognitive function in patients who were deemed to be progression-free. This study showed that patients on the BEV arm had a greater increase of patient-reported symptom burden and more decline of neurocognitive function and quality of life over time compared with patients in the placebo arm.

Preliminary molecular analysis from a subset of tumor tissues suggests that a molecular profile may be able to identify a subgroup of patients that could benefit from BEV in the first-line setting. However, until a patient subgroup can be identified, the results of the study do not support the use of BEV in the first-line setting for glioblastoma.

• © 2013 MD Conference Express®