Drug Safety Developments

Avastin and Other VEGF Inhibitors Linked to Aneurysm and Artery Dissection

New Study Shows Further Evidence of Adverse Events in Association With VEGF Inhibitor Drugs

 

Written by: Lauren Schwab, Legal Assistant

Law Offices of Thomas J. Lamb, P.A.

 

A class of cancer treatment drugs labeled as antiangiogenic agents have been associated with artery dissections and aneurysms.  An arterial dissection occurs when there is a tear in the lining of an artery, which can cause blood to pool in the area, potentially leading to the formation of a blood clot.  An aneurysm is an enlargement of an artery caused by a weakening of the artery wall, and while most aneurysms do not show symptoms, if ruptured they can result in internal bleeding or a stroke.

According to the Medpage Today March 2021 article, "Class of Cancer Drug Linked to Aneurysms, Artery Dissections", which focused on the JAMA Oncology study "Association Between Antiangiogenic Drugs Used for Cancer Treatment and Artery Dissections or Aneurysms", this specific class of cancer drugs are 3 times more likely to result in an artery dissection or aneurysm than other cancer drugs:

The analysis of the WHO's VigiBase database found that artery dissections or aneurysms were nearly three times as likely to be reported with antiangiogenic agents as compared with other cancer drugs (proportional reporting ratio 2.76, 95% CI 2.48-3.07; Bayesian information component 1.14, 95% credibility interval 0.99-1.25), reported Pernelle Noize, PharmD, PhD, of Bordeaux University Hospital in France, and colleagues.

Among nearly 500 cases of artery dissections or aneurysms associated with these agents, 88.3% were serious, with 24.3% being fatal, 17.8% considered life-threatening, and 24.7% leading to or prolonging hospitalization, according to the findings in JAMA Oncology.

The same Medpage Today article lists several vascular endothelial growth factor (VEGF) inhibitors as being associated with artery dissections or aneurysms, including Avastin, Sutent, and Ofev:

Fourteen individual agents in the class were associated with artery dissections or aneurysms, including the VEGF inhibitors bevacizumab (Avastin) and ramucirumab (Cyramza); the tyrosine kinase inhibitors (TKIs) sunitinib (Sutent), pazopanib (Votrient), axitinib (Inlyta), nintedanib (Ofev), and lenvatinib (Lenvima); the multikinase inhibitor cabozantinib (Cometriq, Cabometyx); and the mTOR inhibitor everolimus (Afinitor). A number of these agents were also associated with both aortic- and cerebral-specific events.

VEGF inhibitors were the most commonly involved antiangiogenic agent (51.4%), followed by TKIs (35.8%) and mTOR inhibitors (11.5%). For individual agents, bevacizumab (44.9%), sunitinib (14.4%), and everolimus (11.1%) were most frequently associated with these events. Median time to onset was 89 days (interquartile range 27-212) where data were available.

 

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The data from this antiangiogenic drug study aligns with the July 2020 Drug Safety Update from the United Kingdom's Medicines and Healthcare products Regulatory Agency (MHRA) previously reported on our Drug Injury Watch Blog in August 2020, "Vascular Endothelial Growth Factor (VEGF) Inhibitors: Increased Risk Of Aneurysm And Artery Dissection".  The MHRA update required a warning label to be added to all VEGF inhibitors advising of the risks of aneurysm and artery dissection associated with this class of drugs.

This same class of drugs appeared on the January through March 2020 FDA watch list as having a potential signal of serious risk of aneurysm and artery dissection.  As of June 2020, the FDA was evaluating the need for regulatory action.  This class of drugs did not appear on the following three quarterly reports from the FDA, and whether or not regulatory action will be taken against these drugs is unclear at the present time.

We will continue to monitor the safety profiles for these VEGF inhibitors, including whether the FDA mandates any label changes which add warnings about an increased risk of aneurysm and artery dissection for this class of drugs.

 

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Cancer drug Avastin tied to 2 cases of flesh-eating disease in Canada

Quoted from http://www.cbc.ca/news/health/story/2013/05/02/avastin-flesh-eating-disease.html

Cancer drug Avastin tied to 2 cases of flesh-eating disease in Canada

Health Canada issues caution to users, echoing U.S. warning

CBC News

Posted: May 2, 2013 11:05 AM ET

The cancer-treatment drug Avastin has been linked to 52 cases of flesh-eating disease worldwide, including one that resulted in death in Canada.

Health Canada issued a warning today in conjunction with the drug's manufacturer, Hoffmann-La Roche Ltd., echoing an earlier one from the U.S. Food and Drug Administration. It offered no specific details on two Canadian cases.

Avastin is used either alone to treat a particular type of brain cancer (glioblastoma), or in combination with chemotherapy to treat cancers that have spread to other parts of the body such as colon, rectal and lung cancer.

[Article continues at original source]

Doctors Grow Wary of Avastin for Eye Treatment

Quoted from http://prescriptions.blogs.nytimes.com/2011/10/04/doctors-grow-wary-of-avastin-for-eye-treatment/

Doctors Grow Wary of Avastin for Eye Treatment

By ANDREW POLLACK

October 4, 2011, 9:51 am

Dr. Robert Feig, a retina specialist in Brooklyn and the Bronx, says he wants to save patients and Medicare money by treating eye diseases with a drug that costs $50 a dose, rather than one that costs $2,000 a dose.

But three recent incidents around the country in which a total of 21 patients lost some or all vision in the affected eye after injections of the less expensive drug have made him fearful of a malpractice lawsuit, should something similar happen at his practice.

“Why would I want to risk my family to save America $1,950 a dose?” asked Dr. Feig. So even though he laments it, he is starting to use more of the expensive product, Lucentis, instead of the cheaper one, Avastin.

Similar trade-offs of cost versus perceived risk are being weighed across the country.

[Article continues at original source]

Avastin Injections Are Said to Cause Blindness

Quoted from http://www.nytimes.com/2011/08/31/health/31drug.html

Avastin Injections Are Reported to Cause Blindness

By ANDREW POLLACK

Published: August 30, 2011

At least 16 people in two states have gotten severe eye infections, and some have been blinded, from injections of the drug Avastin, according to health authorities and to lawyers representing the patients.

The cancer drug Avastin has been used by some doctors to treat macular degeneration, an off-label application.

The incidents, in Florida and Tennessee, demonstrate the risks associated with the money-saving practice of injecting Avastin into the eye to treat the wet form of age-related macular degeneration, a common cause of severe vision loss in the elderly.

Avastin, sold by Genentech, is approved to treat cancer, not eye disease. But many retina specialists use Avastin off label because it costs only about $50 an injection, compared with $2,000 for Lucentis, another Genentech drug that has the same mode of action and is approved as an eye treatment.

The off-label use of Avastin has saved Medicare and patients hundreds of millions of dollars a year. But dividing a vial of Avastin into numerous tiny doses for injection into the eye introduces the risk of bacterial contamination. That is apparently what has happened in the cases in Florida and Tennessee.

The Food and Drug Administration issued an alert late Tuesday saying that at least 12 patients in Miami, treated at three clinics, had suffered eye inflammations. While all had impaired eyesight to begin with, some lost all remaining vision in the treated eye, the agency said.

[Article continues at original source]

Avastin May Cause Kidney Damage

Quoted from http://www.latimes.com/news/health/sns-health-avastin-kidney-damage,0,4630582.story

Avastin May Cause Kidney Damage

Kidney problems are the second serious condition linked to the cancer drug. Last year it was found that some patients on Avastin were at elevated risk of intestinal perforations.

Delthia Rick

McClatchy Tribune

June 30, 2010

A widely prescribed cancer drug noted for its ability to choke off blood vessels that help tumors grow can cause significant kidney damage in some patients, a team of Long Island scientists has found.

Kidney problems are the second serious condition linked to Avastin and pinpointed in research conducted by Dr. Shenghong Wu and colleagues at Stony Brook University Medical Center. Last year Wu and his team found some patients on the drug were at elevated risk of intestinal perforations.

"This is a drug we use clinically for a lot of tumors - lung cancer, kidney cancer, breast cancer," Wu said in an interview. "The safety is something we are researching. But this drug is used successfully and that is why we are studying it."

Reporting in this month's issue of the Journal of the American Society of Nephrology, Wu wrote that patients on Avastin were at increased risk of severe protein loss from the kidneys, which can lead to permanent damage. Overall, patients on Avastin were at a fourfold risk for protein loss and kidney damage, depending on dosage and the type of cancer.

In terms of incidence, 10 percent of patients being treated with the drug for kidney cancer suffered organ damage and were at highest risk.

[Article continues at original source]