October 5, 2011 — Revised labeling for bevacizumab (Avastin) contains information on the risk for ovarian failure and osteonecrosis of the jaw. It also contains new details on the risk for venous thromboembolic events (VTEs).
The US Food and Drug Administration announced on October 4 that the changes were made to the drug's package insert on September 30.
Ovarian Failure
The new label instructs physicians to inform females of reproductive potential before they start treatment with bevacizumab that there is a risk for ovarian failure.
The data for this warning come from a subset of 179 women taking part in a study investigating bevacizumab in combination with a modified infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) 6 regimen for adjuvant stage 2 and 3 colorectal cancer, a use for which the drug is not approved (its indication for colorectal cancer is for metastatic disease).
In this study, new cases of ovarian failure were identified in 34% of women (32 of 95) being treated with bevacizumab plus chemotherapy and only in 2% of women (2 of 84) being treated with chemotherapy alone (relative risk, 14; 95% confidence interval, 4 to 53). After the discontinuation of bevacizumab treatment, recovery of ovarian function was demonstrated in 22% of these women.
Osteonecrosis of the Jaw
Osteonecrosis of the jaw is a known adverse effect of bisphosphonate therapy; the new label notes that it has also been reported in patients receiving bevacizumab but not bisphosphonates in the postmarketing setting.
The pathogenesis is unclear, but it is possible that the antiangiogenic properties of bevacizumab result in bone tissue vascularization, which could lead to ischemic changes in the microvasculature of the jaw and result in osteonecrosis, the label explains.
Patients on Anticoagulants
Increased risk for a VTE has already been reported with bevacizumab, but a new section of the label notes that patients who have experienced a VTE while taking bevacizumab and who are now being treated with anticoagulants continue to be at increased risk for further VTEs.
These data come from a study conducted in 1401 patients with metastatic colorectal cancer, an approved indication for the drug. The overall incidence of a first VTE was higher in patients being treated with bevacizumab plus chemotherapy than in those being treated with chemotherapy alone (13.5% vs 9.6%).
Among those who developed a first VTE, 116 were treated with anticoagulants (73 on bevacizumab plus chemotherapy and 43 on chemotherapy alone). In this subgroup of patients, the overall incidence of subsequent VTEs was higher in patients receiving bevacizumab (31.5% vs 25.6%); the overall incidence of bleeding was also higher (27.4% vs 20.9%).
The US Food and Drug Administration announced on October 4 that the changes were made to the drug's package insert on September 30.
Ovarian Failure
The new label instructs physicians to inform females of reproductive potential before they start treatment with bevacizumab that there is a risk for ovarian failure.
The data for this warning come from a subset of 179 women taking part in a study investigating bevacizumab in combination with a modified infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) 6 regimen for adjuvant stage 2 and 3 colorectal cancer, a use for which the drug is not approved (its indication for colorectal cancer is for metastatic disease).
In this study, new cases of ovarian failure were identified in 34% of women (32 of 95) being treated with bevacizumab plus chemotherapy and only in 2% of women (2 of 84) being treated with chemotherapy alone (relative risk, 14; 95% confidence interval, 4 to 53). After the discontinuation of bevacizumab treatment, recovery of ovarian function was demonstrated in 22% of these women.
Osteonecrosis of the Jaw
Osteonecrosis of the jaw is a known adverse effect of bisphosphonate therapy; the new label notes that it has also been reported in patients receiving bevacizumab but not bisphosphonates in the postmarketing setting.
The pathogenesis is unclear, but it is possible that the antiangiogenic properties of bevacizumab result in bone tissue vascularization, which could lead to ischemic changes in the microvasculature of the jaw and result in osteonecrosis, the label explains.
Patients on Anticoagulants
Increased risk for a VTE has already been reported with bevacizumab, but a new section of the label notes that patients who have experienced a VTE while taking bevacizumab and who are now being treated with anticoagulants continue to be at increased risk for further VTEs.
These data come from a study conducted in 1401 patients with metastatic colorectal cancer, an approved indication for the drug. The overall incidence of a first VTE was higher in patients being treated with bevacizumab plus chemotherapy than in those being treated with chemotherapy alone (13.5% vs 9.6%).
Among those who developed a first VTE, 116 were treated with anticoagulants (73 on bevacizumab plus chemotherapy and 43 on chemotherapy alone). In this subgroup of patients, the overall incidence of subsequent VTEs was higher in patients receiving bevacizumab (31.5% vs 25.6%); the overall incidence of bleeding was also higher (27.4% vs 20.9%).
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