FDA: Avastin Can Cause Ovarian Failure

FDA LogoThe FDA has changed the package insert for Avastin® (bevacizumab) to include information about newly identified risks for the drug including

  • Loss of ovarian function (ovarian failure).
  • Bone death in the jaw (osteonecrosis).
  • Bleeding and additional blood clots in patients who have already had a clot in their veins while on Avastin.

Changes to the Avastin label were announced on September 30, 2011.

Ovarian Failure

Women with  stage II or III colon cancer who were getting Avastin in combination with chemotherapy during a clinical trial had reduced ovarian function compared to women who were only on chemotherapy.

Women with ovarian failure no longer had menstrual periods or had high levels of a hormone associated with menopause. Follicle stimulating hormones (FSH) blood levels were equal to or above 30.

Among 179 women in a subset of a clinical study, 84 were on FOLFOX chemotherapy alone and 95 received both FOLFOX and Avastin.

  • 2% of the chemo only group had ovarian failure during treatment compared to
  • 34% of those receiving chemo and Avastin.
  • Only 1 in 5 of the women with ovarian failure (22%) started menstruating again and had their FSH levels fall back below 30 during post treatment visits.
  • According to FDA, “Long term effects of Avastin exposure on fertility are unknown.”

Avastin Warnings and Precautions now includes:

Inform females of reproductive potential of the risk of ovarian failure prior to starting treatment with Avastin.

Avastin is not labeled to treat stage II or III colon cancer and failed to improve 3 year disease free survival in two clinical trials — NSABP C-08 and AVANT.

Osteonecrosis of the Jaw

Since Avastin has been on the market, there have been reports of lesions in patient’s mouth that don’t heal.  The jawbones literally die leading to pain and infection.  These patients were not on bisphosphonates, drugs previously linked to jaw osteonecrosis.  Bisphosphonates are used  to prevent bone loss and in some cancer treatments.

It is possible that changes in blood vessels in the jaw led to poor blood supply to the bones and their deterioration.

Osteonecrosis of the jaw has been added to the Adverse Events section of the package insert.

Venous Thromboembolic and Bleeding Events for Patients Receiving Anti-Coagulation

In clinical trials, patients who were taking Avastin, experienced a blood clot in a vein (venous thromboembolic event or VTE) and were on anticoagulant medicine to prevent more clots had higher rates of both further VTEs and bleeding than patients on chemotherapy alone.

In a trial of 1,400 patients with metastatic colorectal cancer there was a higher percentage of first VTE, subsequent VTE, and bleeding after VTE in the trial arms that contained Avastin added to chemotherapy.

  • 13.5 percent of patients in the Avastin arms had an initial VTE compared to 9.6 percent of those only getting chemotherapy.

There were 116 patients who were put on anticoagulant medicine after their first blood clot — 73 on Avastin and 43 on chemotherapy alone:

  • 31.5 percent had another blood clot in a vein while on Avastin compared to 25.6 percent only on chemo.
  • 27.4 percent had bleeding compared to 20.9 percent of patients in the trial arms without Avastin.

This information was added to the Clinical Trial Experience section of the package insert.

What This Means for Patients

Avastin is a helpful addition to chemotherapy for people with advanced colorectal cancer. It improves survival time over chemotherapy alone in both first and second line treatment of stage IV disease.

However, patients and their doctors need to be aware of potential serious side effects as they make treatment decisions.

They also need to watch for adverse events associated with Avastin, including blood clots and osteonecrosis of the jaw.

Women who still are able to have children need to know that Avastin may affect their future fertility.

Leave a Reply

Your email address will not be published. Required fields are marked *

You may use these HTML tags and attributes: <a href="" title=""> <abbr title=""> <acronym title=""> <b> <blockquote cite=""> <cite> <code> <del datetime=""> <em> <i> <q cite=""> <s> <strike> <strong>