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Experts Debate Value of Bevacizumab in Newly Diagnosed Glioblastoma

August 2013 Vol 6, No 6 Special Issue

Chicago, IL—At a plenary session of ASCO 2013, investigators of the phase 3 Radiation Therapy Oncology Group (RTOG) 0825 trial reported that bevacizumab (Avastin) did not improve overall survival (OS) in patients with newly diagnosed glioblastoma, but it did extend progression-free survival (PFS).

Mark R. Gilbert, MD, Professor and Deputy Chairman, Department of Neuro-Oncology, University of Texas M.D. Anderson Cancer Center, Houston, said that although bevacizumab is beneficial in patients with recurrent disease, when added to standard of care, it did not improve OS and, therefore, the study failed to meet its prespecified target.

“Molecular profiling studies may uncover tumor subsets that identify patients benefiting from first-line bevacizumab, but until this subgroup has been defined, these results do not support the use of bevacizumab for newly diagnosed glioblastoma,” Dr Gilbert said.

The RTOG 0825 trial evaluated the use of first-line or early bevacizumab therapy in 637 patients with newly diagnosed glioblastoma who received chemoradiation therapy plus temozolomide and placebo (ie, standard of care) or chemoradiation therapy plus temozolomide and bevacizumab 10 mg/kg every 2 weeks. At disease progression, 41% of patients in the control arm crossed over to the bevacizumab arm (per study design).
The coprimary end points were OS and PFS, with statistically significant P values of .046 for OS and .004 for PFS.

After a median follow-up of 20.5 months, the median OS was 15.7 months with bevacizumab versus 16.1 months with standard therapy (hazard ratio [HR], 1.13; P = .021), and the median PFS was 10.7 months versus 7.3 months, respectively (HR, 0.79; P = .007).

In a prespecified analysis of subgroups by MGMT promoter methylation and 9-gene signature, patients with methylated status benefited from bevacizumab. In the MGMT methylation group, the median OS was 23.2 months versus 14.3 months for patients with MGMT unmethylated status (P <.001), and the median PFS was 14.1 months versus 8.2 months, respectively (P <.001). The patients with MGMT promoter methylation and a favorable 9-gene signature showed a strong trend toward a worse outcome with bevacizumab, especially for OS.

“There was no definable group with an overall survival benefit with bevacizumab,” Dr Gilbert said. “In addition, symptom burden, neurocognitive function, and quality-of-life data show an overall decline over time on first-line bevacizumab.”

Similar findings were also reported for the comparable AVAglio study. The median OS was 17 months in each arm, and the median PFS was 10.6 months with bevacizumab versus 6.2 months with standard care (P <.001). Of note, unlike the RTOG 0825 trial, health-­related quality of life improved in the AVAglio study with bevacizumab.

Howard A. Fine, MD, Deputy Director, New York University Cancer Institute, NY, who was the discussant at the session, remained optimistic about the role of bevacizumab in patients with glioblastoma, noting, “Despite these new data demonstrating its limitations, bevacizumab represents the single most important therapeutic agent in glioblastoma multiforme since temozolomide. Ongoing and future trials will better define how and when it should be optimally used in these patients.”

Last modified: August 30, 2021