Bevacizumab Beyond Progression Extends Survival in Metastatic CRC

CHICAGO – Bevacizumab extended both progression-free and overall survival when it was added to second-line chemotherapy in patients with advanced colorectal cancer, investigators reported at the annual meeting of the American Society of Clinical Oncology.

In a phase III randomized trial, patients with inoperable colorectal cancer (CRC) and disease progression following first-line chemotherapy who received bevacizumab (Avastin) in addition to a second-line regimen had a 1.4-month advantage in overall survival, and 1.6-month-longer progression-free survival than patients who received second-line chemotherapy alone, reported Dr. Dirk Arnold, director of the Hubertus Wald Tumor Center at University Clinic Eppendorf in Hamburg, Germany,

The findings suggest that bevacizumab, which has had mixed results in the treatment of other cancers, plays a significantly favorable role in CRC, Dr. Arnold said.

"This is the first randomized trial to prospectively evaluate bevacizumab beyond first progression. This study confirms that continuing bevacizumab beyond progression while changing chemotherapy is beneficial for patients, and has translated into a significant improvement in overall survival in metastatic colorectal cancer patients, as well as progression-free survival," he said in a briefing.

A total of 820 patients with unresectable metastatic CRC received first-line chemotherapy with either an irinotecan-based or oxaliplatin-based regimen at the treating physician’s discretion plus bevacizumab. At disease progression, the patients were randomly assigned to second-line therapy with the regimen they did not receive up front with or without concomitant bevacizumab.

Median overall survival, the primary end point, was 11.2 months for patients who received bevacizumab, compared with 9.8 months for those who received chemotherapy alone (hazard ratio 0.81, P = .0062). Median progression-free survival was 5.7 months with bevacizumab and 4.1 months without (HR 0.68, P less than .0001).

The overall response rates were 5.4% for the bevacizumab group and 3.9% for the chemotherapy-alone group, a difference that was not statistically significant.

Adverse events with bevacizumab continued in the second line were similar to those of historical controls treated with bevacizumab in either first- or second-line therapy, Dr. Arnold said.

"This provides clearly a new treatment option in the second line for patients who have been pretreated with a bevacizumab combination regimen before," Dr. Arnold said.

"Furthermore, I think these findings indicate that this might also serve as a new model for a treatment approach by multiple treatment lines in metastatic colorectal cancer and across other tumor types, which is currently [being] investigated in other trials," he added.

Dr. Bruce J. Roth, a professor of medicine in the oncology section at Washington University in St. Louis, who was not involved in the study, commented that "medical oncologists have been trained to stop classic cytotoxic therapy at the time of progression, but the issue is a little bit more complicated for anti-VEGF [vascular endothelial growth factor] therapies like bevacizumab, and this issue has been raised in other tumor types."

Dr. Roth moderated the briefing at which Dr. Arnold presented the data.

Dr. Arnold noted that the findings suggest that mechanisms of tumor resistance to cytotoxic agents may be different from those of resistance to antiangiogenic agents, which could explain the additional benefit seen with bevacizumab.

The study, ML 18147, was supported by Roche. Dr. Arnold disclosed serving in a consulting or advisory role for and receiving honoraria from Amgen, Merck Serono, and Roche Diagnostics, and receiving research funding from Roche Diagnostics. Dr. Roth had no disclosures.

CHICAGO – Bevacizumab extended both progression-free and overall survival when it was added to second-line chemotherapy in patients with advanced colorectal cancer, investigators reported at the annual meeting of the American Society of Clinical Oncology.

In a phase III randomized trial, patients with inoperable colorectal cancer (CRC) and disease progression following first-line chemotherapy who received bevacizumab (Avastin) in addition to a second-line regimen had a 1.4-month advantage in overall survival, and 1.6-month-longer progression-free survival than patients who received second-line chemotherapy alone, reported Dr. Dirk Arnold, director of the Hubertus Wald Tumor Center at University Clinic Eppendorf in Hamburg, Germany,

The findings suggest that bevacizumab, which has had mixed results in the treatment of other cancers, plays a significantly favorable role in CRC, Dr. Arnold said.

"This is the first randomized trial to prospectively evaluate bevacizumab beyond first progression. This study confirms that continuing bevacizumab beyond progression while changing chemotherapy is beneficial for patients, and has translated into a significant improvement in overall survival in metastatic colorectal cancer patients, as well as progression-free survival," he said in a briefing.

A total of 820 patients with unresectable metastatic CRC received first-line chemotherapy with either an irinotecan-based or oxaliplatin-based regimen at the treating physician’s discretion plus bevacizumab. At disease progression, the patients were randomly assigned to second-line therapy with the regimen they did not receive up front with or without concomitant bevacizumab.

Median overall survival, the primary end point, was 11.2 months for patients who received bevacizumab, compared with 9.8 months for those who received chemotherapy alone (hazard ratio 0.81, P = .0062). Median progression-free survival was 5.7 months with bevacizumab and 4.1 months without (HR 0.68, P less than .0001).

The overall response rates were 5.4% for the bevacizumab group and 3.9% for the chemotherapy-alone group, a difference that was not statistically significant.

Adverse events with bevacizumab continued in the second line were similar to those of historical controls treated with bevacizumab in either first- or second-line therapy, Dr. Arnold said.

"This provides clearly a new treatment option in the second line for patients who have been pretreated with a bevacizumab combination regimen before," Dr. Arnold said.

"Furthermore, I think these findings indicate that this might also serve as a new model for a treatment approach by multiple treatment lines in metastatic colorectal cancer and across other tumor types, which is currently [being] investigated in other trials," he added.

Dr. Bruce J. Roth, a professor of medicine in the oncology section at Washington University in St. Louis, who was not involved in the study, commented that "medical oncologists have been trained to stop classic cytotoxic therapy at the time of progression, but the issue is a little bit more complicated for anti-VEGF [vascular endothelial growth factor] therapies like bevacizumab, and this issue has been raised in other tumor types."

Dr. Roth moderated the briefing at which Dr. Arnold presented the data.

Dr. Arnold noted that the findings suggest that mechanisms of tumor resistance to cytotoxic agents may be different from those of resistance to antiangiogenic agents, which could explain the additional benefit seen with bevacizumab.

The study, ML 18147, was supported by Roche. Dr. Arnold disclosed serving in a consulting or advisory role for and receiving honoraria from Amgen, Merck Serono, and Roche Diagnostics, and receiving research funding from Roche Diagnostics. Dr. Roth had no disclosures.

CHICAGO – Bevacizumab extended both progression-free and overall survival when it was added to second-line chemotherapy in patients with advanced colorectal cancer, investigators reported at the annual meeting of the American Society of Clinical Oncology.

In a phase III randomized trial, patients with inoperable colorectal cancer (CRC) and disease progression following first-line chemotherapy who received bevacizumab (Avastin) in addition to a second-line regimen had a 1.4-month advantage in overall survival, and 1.6-month-longer progression-free survival than patients who received second-line chemotherapy alone, reported Dr. Dirk Arnold, director of the Hubertus Wald Tumor Center at University Clinic Eppendorf in Hamburg, Germany,

The findings suggest that bevacizumab, which has had mixed results in the treatment of other cancers, plays a significantly favorable role in CRC, Dr. Arnold said.

"This is the first randomized trial to prospectively evaluate bevacizumab beyond first progression. This study confirms that continuing bevacizumab beyond progression while changing chemotherapy is beneficial for patients, and has translated into a significant improvement in overall survival in metastatic colorectal cancer patients, as well as progression-free survival," he said in a briefing.

A total of 820 patients with unresectable metastatic CRC received first-line chemotherapy with either an irinotecan-based or oxaliplatin-based regimen at the treating physician’s discretion plus bevacizumab. At disease progression, the patients were randomly assigned to second-line therapy with the regimen they did not receive up front with or without concomitant bevacizumab.

Median overall survival, the primary end point, was 11.2 months for patients who received bevacizumab, compared with 9.8 months for those who received chemotherapy alone (hazard ratio 0.81, P = .0062). Median progression-free survival was 5.7 months with bevacizumab and 4.1 months without (HR 0.68, P less than .0001).

The overall response rates were 5.4% for the bevacizumab group and 3.9% for the chemotherapy-alone group, a difference that was not statistically significant.

Adverse events with bevacizumab continued in the second line were similar to those of historical controls treated with bevacizumab in either first- or second-line therapy, Dr. Arnold said.

"This provides clearly a new treatment option in the second line for patients who have been pretreated with a bevacizumab combination regimen before," Dr. Arnold said.

"Furthermore, I think these findings indicate that this might also serve as a new model for a treatment approach by multiple treatment lines in metastatic colorectal cancer and across other tumor types, which is currently [being] investigated in other trials," he added.

Dr. Bruce J. Roth, a professor of medicine in the oncology section at Washington University in St. Louis, who was not involved in the study, commented that "medical oncologists have been trained to stop classic cytotoxic therapy at the time of progression, but the issue is a little bit more complicated for anti-VEGF [vascular endothelial growth factor] therapies like bevacizumab, and this issue has been raised in other tumor types."

Dr. Roth moderated the briefing at which Dr. Arnold presented the data.

Dr. Arnold noted that the findings suggest that mechanisms of tumor resistance to cytotoxic agents may be different from those of resistance to antiangiogenic agents, which could explain the additional benefit seen with bevacizumab.

The study, ML 18147, was supported by Roche. Dr. Arnold disclosed serving in a consulting or advisory role for and receiving honoraria from Amgen, Merck Serono, and Roche Diagnostics, and receiving research funding from Roche Diagnostics. Dr. Roth had no disclosures.