Bevacizumab-Irinotecan Data Hold Up in Recurrent GBM

Major Finding: The 12-month rate of survival was 38% with both bevacizumab alone and bevacizumab plus irinotecan in updated analyses, and no new adverse effects were noted.

Data Source: A randomized, noncomparative, open-label phase II trial among 167 patients with relapsed glioblastoma multiforme (the BRAIN trial).

Disclosures: Genentech sponsored the trial. Some of the investigators are employees of or consultants to Genentech, or have received honoraria or research funding from the company. Dr. Brandes disclosed having a consultant or advisory role with and receiving honoraria from Roche, which owns Genentech.

CHICAGO — Bevacizumab, alone or in combination with irinotecan, is generally safe and active in patients with relapsed glioblastoma, according to updated results of the phase II BRAIN trial.

“Up to 16% of patients who received bevacizumab-based therapy remained alive at 30 months,” lead investigator Dr. Timothy Cloughesy reported. “The incidence of selected [adverse events] in the updated safety data was consistent with what was previously reported—there were no new safety signals that were identified.”

The Study to Evaluate Bevacizumab Alone or in Combination With Irinotecan for Treatment of Glioblastoma Multiforme (BRAIN) trial's efficacy results compare favorably with those of similar trials testing other regimens, Dr. Cloughesy said: the 12-month survival rate was 38% whereas it has been 14%-27% with cytotoxic agents such as temozolomide (Temo-dar) or lomustine (CCNU).

Sorting out the specific contributions of bevacizumab (Avastin) and irinotecan (Camptosar) to the observed outcomes is difficult because of the trial's design, he said. However, “when we look at what is providing the majority of the effect that we are seeing, I think it is coming from bevacizumab.”

The multicenter trial, sponsored by Genentech (manufacturer of bevacizumab), opened in July 2006 to patients with glioblastoma in first or second relapse who had previously received radiation therapy and temozolomide.

They were randomly assigned in nearly equal numbers to open-label treatment with bevacizumab alone or bevacizumab plus irinotecan.

Updated results were based on data cutoffs of July 2008 (treatment exposure, safety, and median survival) and July 2009 (survival rates), according to Dr. Cloughesy. The 167 enrolled patients had a median age of about 55 years. The majority were male (68%) and white (90%), and experiencing a first relapse (81%). Progression occurred in 59% of the patients in the bevacizumab arm, and these patients went on to receive the combination therapy.

The median number of bevacizumab doses received was 9 in the bevacizumab group and 11 in the bevacizumab-irinotecan group during the main phase of the trial, reported Dr. Cloughesy, director of the neuro-oncology program and a clinical professor at the Ronald Reagan UCLA Medical Center in Los Angeles. The median number was three during the post-progression phase.

The updated safety data showed little change from the initial results, he said. Some 51% of patients in the bevacizumab group and 71% in the bevacizumab-irinotecan group had adverse events of grade 3 or higher. Hypertension was the predominant event with monotherapy (11%), whereas venous thromboembolism was the predominant event with combination therapy (10%).

“The things that… we are concerned about with regard to patients who are taking anti-VEGF [vascular endothelial growth factor] therapy—cerebral hemorrhage, wound healing, arterial thrombotic embolism, and gastrointestinal perforation—these all stayed fairly low,” he commented. These events occurred at a severity of grade 3 or higher in only 0%-3.6% of patients.

Median overall survival was 9.3 months with bevacizumab alone and 8.9 months with both drugs. The proportion of patients still alive was 38% in each arm at 12 months; 24% and 18%, respectively, at 18 months; 16% and 17%, at 24 months; and 11% and 16%, at 30 months.

Dr. Alba A. Brandes, a medical oncologist at Azienda USL in Bologna, Italy, noted that the trial's size and promising results were strengths, but said its evaluation criteria and lack of a standard control arm and biomarker studies were weaknesses.

“Bevacizumab has brought light into the treatment of recurrent GBM, a setting with scarce options and dismal results,” she commented. “The advantage of bevacizumab over classical cytotoxics seems to be in the range of 2 to 3 months. That represents a prolongation of 30% in survival at recurrence,” said Dr. Brandes. “However, this advantage should be proven in phase III trials.”

We think the majority of the effect that we are seeing with the two drugs in this trial comes from bevacizumab.

Source DR. CLOUGHESY

Major Finding: The 12-month rate of survival was 38% with both bevacizumab alone and bevacizumab plus irinotecan in updated analyses, and no new adverse effects were noted.

Data Source: A randomized, noncomparative, open-label phase II trial among 167 patients with relapsed glioblastoma multiforme (the BRAIN trial).

Disclosures: Genentech sponsored the trial. Some of the investigators are employees of or consultants to Genentech, or have received honoraria or research funding from the company. Dr. Brandes disclosed having a consultant or advisory role with and receiving honoraria from Roche, which owns Genentech.

CHICAGO — Bevacizumab, alone or in combination with irinotecan, is generally safe and active in patients with relapsed glioblastoma, according to updated results of the phase II BRAIN trial.

“Up to 16% of patients who received bevacizumab-based therapy remained alive at 30 months,” lead investigator Dr. Timothy Cloughesy reported. “The incidence of selected [adverse events] in the updated safety data was consistent with what was previously reported—there were no new safety signals that were identified.”

The Study to Evaluate Bevacizumab Alone or in Combination With Irinotecan for Treatment of Glioblastoma Multiforme (BRAIN) trial's efficacy results compare favorably with those of similar trials testing other regimens, Dr. Cloughesy said: the 12-month survival rate was 38% whereas it has been 14%-27% with cytotoxic agents such as temozolomide (Temo-dar) or lomustine (CCNU).

Sorting out the specific contributions of bevacizumab (Avastin) and irinotecan (Camptosar) to the observed outcomes is difficult because of the trial's design, he said. However, “when we look at what is providing the majority of the effect that we are seeing, I think it is coming from bevacizumab.”

The multicenter trial, sponsored by Genentech (manufacturer of bevacizumab), opened in July 2006 to patients with glioblastoma in first or second relapse who had previously received radiation therapy and temozolomide.

They were randomly assigned in nearly equal numbers to open-label treatment with bevacizumab alone or bevacizumab plus irinotecan.

Updated results were based on data cutoffs of July 2008 (treatment exposure, safety, and median survival) and July 2009 (survival rates), according to Dr. Cloughesy. The 167 enrolled patients had a median age of about 55 years. The majority were male (68%) and white (90%), and experiencing a first relapse (81%). Progression occurred in 59% of the patients in the bevacizumab arm, and these patients went on to receive the combination therapy.

The median number of bevacizumab doses received was 9 in the bevacizumab group and 11 in the bevacizumab-irinotecan group during the main phase of the trial, reported Dr. Cloughesy, director of the neuro-oncology program and a clinical professor at the Ronald Reagan UCLA Medical Center in Los Angeles. The median number was three during the post-progression phase.

The updated safety data showed little change from the initial results, he said. Some 51% of patients in the bevacizumab group and 71% in the bevacizumab-irinotecan group had adverse events of grade 3 or higher. Hypertension was the predominant event with monotherapy (11%), whereas venous thromboembolism was the predominant event with combination therapy (10%).

“The things that… we are concerned about with regard to patients who are taking anti-VEGF [vascular endothelial growth factor] therapy—cerebral hemorrhage, wound healing, arterial thrombotic embolism, and gastrointestinal perforation—these all stayed fairly low,” he commented. These events occurred at a severity of grade 3 or higher in only 0%-3.6% of patients.

Median overall survival was 9.3 months with bevacizumab alone and 8.9 months with both drugs. The proportion of patients still alive was 38% in each arm at 12 months; 24% and 18%, respectively, at 18 months; 16% and 17%, at 24 months; and 11% and 16%, at 30 months.

Dr. Alba A. Brandes, a medical oncologist at Azienda USL in Bologna, Italy, noted that the trial's size and promising results were strengths, but said its evaluation criteria and lack of a standard control arm and biomarker studies were weaknesses.

“Bevacizumab has brought light into the treatment of recurrent GBM, a setting with scarce options and dismal results,” she commented. “The advantage of bevacizumab over classical cytotoxics seems to be in the range of 2 to 3 months. That represents a prolongation of 30% in survival at recurrence,” said Dr. Brandes. “However, this advantage should be proven in phase III trials.”

We think the majority of the effect that we are seeing with the two drugs in this trial comes from bevacizumab.

Source DR. CLOUGHESY

Major Finding: The 12-month rate of survival was 38% with both bevacizumab alone and bevacizumab plus irinotecan in updated analyses, and no new adverse effects were noted.

Data Source: A randomized, noncomparative, open-label phase II trial among 167 patients with relapsed glioblastoma multiforme (the BRAIN trial).

Disclosures: Genentech sponsored the trial. Some of the investigators are employees of or consultants to Genentech, or have received honoraria or research funding from the company. Dr. Brandes disclosed having a consultant or advisory role with and receiving honoraria from Roche, which owns Genentech.

CHICAGO — Bevacizumab, alone or in combination with irinotecan, is generally safe and active in patients with relapsed glioblastoma, according to updated results of the phase II BRAIN trial.

“Up to 16% of patients who received bevacizumab-based therapy remained alive at 30 months,” lead investigator Dr. Timothy Cloughesy reported. “The incidence of selected [adverse events] in the updated safety data was consistent with what was previously reported—there were no new safety signals that were identified.”

The Study to Evaluate Bevacizumab Alone or in Combination With Irinotecan for Treatment of Glioblastoma Multiforme (BRAIN) trial's efficacy results compare favorably with those of similar trials testing other regimens, Dr. Cloughesy said: the 12-month survival rate was 38% whereas it has been 14%-27% with cytotoxic agents such as temozolomide (Temo-dar) or lomustine (CCNU).

Sorting out the specific contributions of bevacizumab (Avastin) and irinotecan (Camptosar) to the observed outcomes is difficult because of the trial's design, he said. However, “when we look at what is providing the majority of the effect that we are seeing, I think it is coming from bevacizumab.”

The multicenter trial, sponsored by Genentech (manufacturer of bevacizumab), opened in July 2006 to patients with glioblastoma in first or second relapse who had previously received radiation therapy and temozolomide.

They were randomly assigned in nearly equal numbers to open-label treatment with bevacizumab alone or bevacizumab plus irinotecan.

Updated results were based on data cutoffs of July 2008 (treatment exposure, safety, and median survival) and July 2009 (survival rates), according to Dr. Cloughesy. The 167 enrolled patients had a median age of about 55 years. The majority were male (68%) and white (90%), and experiencing a first relapse (81%). Progression occurred in 59% of the patients in the bevacizumab arm, and these patients went on to receive the combination therapy.

The median number of bevacizumab doses received was 9 in the bevacizumab group and 11 in the bevacizumab-irinotecan group during the main phase of the trial, reported Dr. Cloughesy, director of the neuro-oncology program and a clinical professor at the Ronald Reagan UCLA Medical Center in Los Angeles. The median number was three during the post-progression phase.

The updated safety data showed little change from the initial results, he said. Some 51% of patients in the bevacizumab group and 71% in the bevacizumab-irinotecan group had adverse events of grade 3 or higher. Hypertension was the predominant event with monotherapy (11%), whereas venous thromboembolism was the predominant event with combination therapy (10%).

“The things that… we are concerned about with regard to patients who are taking anti-VEGF [vascular endothelial growth factor] therapy—cerebral hemorrhage, wound healing, arterial thrombotic embolism, and gastrointestinal perforation—these all stayed fairly low,” he commented. These events occurred at a severity of grade 3 or higher in only 0%-3.6% of patients.

Median overall survival was 9.3 months with bevacizumab alone and 8.9 months with both drugs. The proportion of patients still alive was 38% in each arm at 12 months; 24% and 18%, respectively, at 18 months; 16% and 17%, at 24 months; and 11% and 16%, at 30 months.

Dr. Alba A. Brandes, a medical oncologist at Azienda USL in Bologna, Italy, noted that the trial's size and promising results were strengths, but said its evaluation criteria and lack of a standard control arm and biomarker studies were weaknesses.

“Bevacizumab has brought light into the treatment of recurrent GBM, a setting with scarce options and dismal results,” she commented. “The advantage of bevacizumab over classical cytotoxics seems to be in the range of 2 to 3 months. That represents a prolongation of 30% in survival at recurrence,” said Dr. Brandes. “However, this advantage should be proven in phase III trials.”

We think the majority of the effect that we are seeing with the two drugs in this trial comes from bevacizumab.

Source DR. CLOUGHESY