Breakthrough Cited for Recurrent Glioblastoma

Breakthrough Cited for Recurrent Glioblastoma

By Charles Bankhead , Staff Writer, MedPage Today
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner

Explain to patients that a targeted therapy improved response rate, progression-free survival, and overall survival in patients with recurrent glioblastoma, compared with historical standard therapy. The targeted therapy was not directly compared with standard therapy.
Note that the therapy did not cure the cancer.
Patients with recurrent glioblastoma had dramatic improvement in response, progression-free survival (PFS), and overall survival compared with historical controls when treated with bevacizumab (Avastin) alone or in combination with irinotecan, data from a multicenter trial showed.

The response rate ranged as high as 38%, PFS to 50%, and overall survival to nine months. All of the outcomes represented major improvement over historical data for patients with recurrent glioblastoma, according to an article published online in the Journal of Clinical Oncology.

"This is a huge breakthrough," Timothy Cloughesy, MD, of UCLA, said in a statement. "In all the years we've been treating recurrent glioblastoma using conventional and investigational agents, we've never had anything like the responses we're seeing with Avastin."

The most aggressive malignant primary brain tumor in adults, glioblastoma is usually fatal, despite aggressive therapy that typically includes surgery, radiotherapy, and chemotherapy.

Patients with recurrent glioblastoma have few treatment options, first author Henry Friedman, MD, of Duke University in Durham, N.C., and colleagues said.

In the setting of recurrent glioblastoma, patients often receive irinotecan, although historical response rates have been 15% or lower. Six-month PFS associated with relapsed or progressive glioblastoma is 9% to 21%, and median overall survival is 30 weeks or less, the authors noted.

Overexpression of vascular endothelial growth factor (VEGF) in recurrent glioblastoma correlates with poor prognosis. In a phase II trial conducted at a single center, bevacizumab, a VEGF inhibitor, combined with irinotecan resulted in an overall response rate of 57% and six-month PFS of 46% (J Clin Oncol 2007; 25: 4722-4729).

Seeking to confirm the single-institution data, investigators conducted a multicenter, phase II, randomized, noncomparative trial.

Eligible patients had glioblastoma in first or second relapse and disease progression confirmed by MRI. They were randomized to bevacizumab or bevacizumab plus irinotecan, and treatment continued for a maximum of 104 weeks, or until disease progression or discontinuation.

The authors reported data on 167 patients. Estimated six-month PFS was 42.6% with bevacizumab alone and 50.3% in the combination arm.

Objective responses occurred in 28.2% of patients randomized to monotherapy and 37.8% with combination therapy. Median overall survival was 9.2 months with bevacizumab alone and 8.7 months in patients who received bevacizumab plus irinotecan.

"I think what this tells us is that the majority of the effects we're seeing are due to the Avastin," said Cloughesy.

Irinotecan also added to toxicity, and 65.8% of patients in the combination arm had grade 3+ adverse events compared with 46.4% in the bevacizumab monotherapy arm.

The most common grade 3+ events with bevacizumab alone were hypertension (8.3%) and convulsion (6.0%). In the combination arm, the most common grade 3+ adverse events were convulsion (13.9%), neutropenia (8.9%), and fatigue (8.9%).

Two patients in the bevacizumab arm had grade 1 intracranial hemorrhage, as did three in the combination arm (grades 1, 2, and 4).

Genentech provided support for preparation of the manuscript.

Jane Huang and Maoxia Zheng are employed by Genentech. Friedman, Cloughesy, and coauthors Michael D. Prados, Patrick Y. Wen, Nina Paleologos, Tom Mikkelsen, David Schiff, Lauren E. Abrey, James Vredenburgh, Martin K. Nicholas disclosed relationships with Genentech.

Wen, Mikkelsen, and W. K. Alfred Yung disclosed relationships with Schering-Plough. Yung disclosed a relationship with Novartis. Abrey disclosed a relationship with Pfizer. Coauthors Jane Huang and Maoxia Zheng are Genentech employees.