SNO: Bevacizumab-Irinotecan Combination Boosts Progression-Free Survival in Relapsed Glioblastoma


DALLAS, Nov. 20 -- Half of patients with relapsed glioblastoma multiforme survived for six months without disease progression when treated with bevacizumab (Avastin) and irinotecan (Campto), according to initial results from an ongoing clinical trial.When treated with bevacizumab alone, more than a third of patients reached the six-month mark, Timothy Cloughesy, M.D., of UCLA, reported here at the Society for Neuro-Oncology meeting.
Action Points
Explain to interested patients that combination chemotherapy with bevacizumab and irinotecan has shown promise for improving progression-free survival in glioblastoma multiforme.
Note that the combination remains investigational.
Note also that the findings were reported at a medical conference and should be considered preliminary until they appear in a peer-reviewed journal.
Historical data suggest a six-month progression-free survival of only about 15% for patients with relapsed glioblastoma multiforme.
"These are really dramatic results," Dr. Cloughesy said in an interview. "We are not accustomed to seeing this type of response and progression-free survival in patients with relapsed glioblastoma."
The findings came from a phase II, randomized, open-label clinical trial evaluating the angiogenesis inhibitor bevacizumab alone or in combination with irinotecan. A threefold scientific rationale provided the basis for the investigation:
A recent phase III trial of chemoradiation followed by temozolomide demonstrated a benefit only for glioblastoma patients with the methylated form of the MGMT promoter gene (N Engl J Med 2005; 352: 987-996).
Irinotecan has single-agent activity in glioblastoma multiforme and a different mechanism of action from temozolomide.
Glioblastoma multiforme has elevated expression of vascular endothelial growth factor, the target of bevacizumab.
Results of a small phase II trial demonstrated a six-month progression-free survival of 46% in patients with relapsed glioblastoma multiforme treated with two different bevacizumab-irinotecan regimens (J Clin Oncol 2007; 25: 4722-4729). That trial set the stage for the randomized evaluation of bevacizumab alone or in combination with irinotecan.
Dr. Cloughesy presented the initial results from the trial, which is expected to conclude in 2008. The data comprised 167 patients with glioblastoma multiforme that had relapsed after first- or second-line chemotherapy. All the patients had had prior treatment with temozolomide.
The primary endpoints of the trial were objective response (as assessed by MRI) and six-month progression-free survival. Secondary endpoints included overall survival and safety.
Dr. Cloughesy reported that 18 of 85 patients (21%) had objective responses to bevacizumab alone and 28 of 82 (34%) had responses when treated with bevacizumab plus irinotecan. Six-month progression-free survival was 36% with bevacizumab and 51% with combination therapy.
Adverse events were consistent with previous clinical experience with bevacizumab and irinotecan, said Dr. Cloughesy. The most common grade 3+ events with bevacizumab alone were hypertension (seven patients) and convulsion (five patients). In the combination arm, grade 3+ convulsion occurred in 10 patients and grade 3+ neutropenia in seven.
Two patients had intracranial hemorrhage with bevacizumab alone as did one in the combination arm. Two treatment-emergent deaths occurred with bevacizumab monotherapy and one occurred in the combination arm.
Dr. Cloughesy is an investigator for Genentech, which sponsored the trial.
Primary source: Society of Neuro-Oncology