FDA Approves New Use of Avastin Plus Fluoropyrimidine-Based Chemotherapy in Metastatic Colorectal Cancer
January 23rd, 2013
People who start on Avastin for mCRC can now stay on Avastin after their cancer worsens.
On January 23, 2013, the FDA has approved a new use of Avastin® (bevacizumab) in combination with fluoropyrimidine-based irinotecan or oxaliplatin chemotherapy for people with metastatic colorectal cancer (mCRC). The new indication will allow people who received Avastin plus an irinotecan or oxaliplatin containing chemotherapy as an initial treatment (first-line) for mCRC to conti
News in brief
- People now have the option to continue with Avastin plus a new chemotherapy after their cancer worsens, which may help them live longer than changing to the new chemotherapy alone.
- This is the third approval for Avastin in mCRC based on improved overall survival in a pivotal study.
BOXED WARNINGS and Additional Important Safety Information
People receiving Avastin may experience side effects. In clinical trials, some people treated with Avastin experienced serious and sometimes fatal side effects, including:
Gastrointestinal (GI) perforation:
- Treatment with Avastin can result in the development of a serious side effect called GI perforation, which is the development of a hole in the stomach, small intestine, or large intestine
- In clinical trials, this event occurred in more people who received Avastin than in the comparison group (up to 3.2%)
- In some cases, GI perforation resulted in fatality. Avastin therapy should be permanently stopped if GI perforation occurs
Surgery and wound healing problems:
- Treatment with Avastin can lead to slow or incomplete wound healing (for example, when a surgical incision has trouble healing or staying closed). In some cases, this event resulted in fatality
- Surgery and wound healing problems occurred more often in people who received Avastin than in the comparison group. In a controlled clinical trial, in patients with metastatic colorectal cancer who had surgery during the course of treatment, the incidence of wound healing complications, including serious and fatal complications, was 15 percent for patients who received Avastin and four percent for patients who did not receive Avastin
- Avastin therapy should not be started for at least 28 days after surgery and until the surgical wound is fully healed. The length of time between stopping Avastin and having voluntary surgery without the risk of wound healing problems following surgery has not been determined
- Treatment with Avastin should be stopped at least 28 days before voluntary surgery and in people with wound healing problems following surgery that require medical treatment. Treatment with Avastin should be stopped in patients with slow or incomplete wound healing
- Treatment with Avastin can result in serious or fatal bleeding, including coughing up blood, bleeding in the stomach, vomiting of blood, bleeding in the brain, nosebleeds, and vaginal bleeding. These events occurred up to five times more often in people who received Avastin compared to patients who received only chemotherapy
- Across cancer types, 0.4 percent to 6.9 percent of people who received Avastin experienced severe to fatal bleeding. People who have recently coughed up blood (greater than or equal to a half teaspoon of red blood) or have serious bleeding should not receive Avastin. Treatment with Avastin should be permanently stopped if serious bleeding occurs
Additional serious adverse events
In clinical trials for different cancer types, there were additional serious and sometimes fatal side effects that occurred in more people who received Avastin than in those in the comparison group.
- The formation of an abnormal passage in the body (GI and non-GI fistula formation) was seen in up to 2% of people. In a study of patients with cervical cancer, formation of an abnormal passage between the vagina and GI tract was seen in 8.3% of people
- Severe to life-threatening stroke or heart problems were seen in 2.6 percent of people
- Too much protein in the urine that led to kidney problems was seen in ≤1% percent of people
- Additional serious side effects that occurred in more people who received Avastin than those in the comparison group included
- severe to life-threatening blood clots (VTE), up to 10.6%
- severe to life threatening high blood pressure, which was seen in 5% to 18% of people
- nervous system and vision disturbances (Posterior Reversible Encephalopathy Syndrome) which was seen in less than 0.5% of people
- Infusion reactions with the first dose of Avastin were uncommon and occurred in less than three percent of people, and severe reactions occurred in 0.2 percent of people
- Avastin can cause fertility issues for women. Avastin could cause a woman’s ovaries to stop working and may impair her ability to have children
- Avoid use in patients with ovarian cancer who have evidence of recto-sigmoid involvement by pelvic examination or bowel involvement on CT scan or clinical symptoms of bowel obstruction
Common side effects that occurred in more than 10% of people who received Avastin for different cancer types, and at least twice the rate of the comparison group, were nosebleeds, headache, high blood pressure, inflammation of the nose, too much protein in the urine, taste change, dry skin, rectal bleeding, tear production disorder, back pain, and inflammation of the skin (exfoliative dermatitis).
Across all trials, treatment with Avastin was permanently stopped in 8.4% to 21% of people because of side effects.
Patients who are pregnant or thinking of becoming pregnant should talk with their doctor about the potential risk of loss of the pregnancy or the potential risk of Avastin to the fetus during and following Avastin therapy, and the need to continue an effective birth control method for at least six months following the last dose of Avastin.
Women should be advised to discontinue nursing or discontinue treatment with Avastin, taking into account the importance of Avastin to the mother.
Report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch.
Report side effects to Genentech at (888) 835-2555.
For full Prescribing Information and Boxed WARNINGS on Avastin, please visit http://www.avastin.com.