FDA Approves New Use of Avastin Plus Chemotherapy for People with Metastatic Colorectal Cancer

SOUTH SAN FRANCISCO, Calif.--()--Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that the U.S. Food and Drug Administration (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 continue to receive Avastin plus a different irinotecan or oxaliplatin containing chemotherapy after their cancer worsens (second-line treatment).

“The majority of people diagnosed with metastatic colorectal cancer receive Avastin plus chemotherapy as their initial treatment,” said Hal Barron, M.D., chief medical officer and head of Global Product Development. “These 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.”

Avastin in combination with fluoropyrimidine-irinotecan or fluoropyrimidine-oxaliplatin based chemotherapy is now indicated for the second-line treatment of patients with metastatic colorectal cancer who have progressed on a first-line Avastin containing regimen. The approval is based on positive results from the Phase III ML18147 study, which were presented at the 2012 American Society of Clinical Oncology annual meeting and showed that people who continued to receive an Avastin-based regimen after their cancer worsened lived longer than people who switched to chemotherapy alone.

  • The risk of death was reduced by 19 percent for people who received Avastin in combination with standard chemotherapy in both the first- and second-line compared to those who received chemotherapy alone (HR=0.81, p=0.0057). Median overall survival was 11.2 months compared to 9.8 months.
  • The risk of the cancer worsening or death (progression-free survival; PFS) was reduced by 32 percent (HR=0.68, p<0.0001). Median PFS was 5.7 months compared to 4.1 months.
  • Overall survival and PFS were calculated from the time patients were randomized to the second-line treatment.
  • There was no significant difference in response rate between treatment arms.
  • Adverse events (AEs) in ML18147 were consistent with those seen in previous pivotal trials of Avastin in mCRC.

Avastin is the only biologic medicine approved by the FDA to treat people with mCRC in combination with intravenous 5FU-based chemotherapy as an initial treatment, as treatment for people whose cancer worsened after chemotherapy alone, and now as a treatment for people whose cancer has worsened after initial treatment with an Avastin-based regimen. This is the third approval for Avastin in mCRC based on improved overall survival. Avastin is not indicated for adjuvant treatment of colon cancer.

Avastin is approved in Europe in combination with fluoropyrimidine-based chemotherapy for the treatment of adult patients with metastatic carcinoma of the colon or rectum. The European product information has been updated based on the positive results of the Phase III ML18147 study with an implementation date of December 12, 2012, allowing people with mCRC who received Avastin plus chemotherapy as a first-line treatment to continue to receive Avastin plus chemotherapy after their cancer worsens as part of their second-line treatment.

About the ML18147 Study

ML18147 was a randomized, open-label, Phase III multicenter, multinational trial evaluating the efficacy and safety profile of Avastin plus standard second-line chemotherapy in 820 patients with mCRC whose disease had progressed following Avastin plus standard first-line chemotherapy (irinotecan or oxaliplatin-based). Patients were randomized at progression to one of two treatment arms:

  • Arm A: Chemotherapy* plus Avastin (equivalent of 2.5 mg/kg i.v. per week)
  • Arm B: Chemotherapy* alone

*Depending on the first-line chemotherapy backbone (fluoropyrimidine-irinotecan or fluoropyrimidine-oxaliplatin based), the chemotherapy backbone was switched in the second-line setting.

The primary endpoint of the study was overall survival measured from the time patients were randomized to the second-line treatment. The secondary efficacy endpoints of the study included PFS, overall response rate and safety profile.

About Colorectal Cancer

According to the American Cancer Society, colorectal cancer is the third most commonly diagnosed cancer in both men and women in the United States and the third leading cause of cancer deaths. In 2012, more than 143,000 people were diagnosed and nearly 52,000 individuals were projected to die from the disease in the United States. If colorectal cancer spreads (metastasizes) to distant organs, such as the lungs or the liver, five-year survival declines to 12 percent.

About Genentech Access Solutions

Genentech is committed to people having access to our medicines. Genentech Access Solutions is a team of more than 350 Genentech employees who help those who need our medicines. Our knowledgeable and experienced specialists can help patients and medical practices navigate the access and reimbursement process and provide assistance to eligible patients in the United States who do not have insurance coverage or who cannot afford their out-of-pocket co-pay costs. For more information, please visit http://www.Genentech-Access.com.

About Avastin

Avastin is a prescription-only medicine that is a solution for intravenous infusion. It is a biologic antibody designed to specifically bind to a protein called vascular endothelial growth factor (VEGF) that plays an important role throughout the lifecycle of the tumor to develop and maintain blood vessels, a process known as angiogenesis. Avastin is designed to interfere with the tumor blood supply by directly binding to the VEGF protein to prevent interactions with receptors on blood vessel cells. The tumor blood supply is thought to be critical to a tumor's ability to grow and spread in the body (metastasize).

Avastin Indications in Metastatic Colorectal Cancer:

  • Avastin is indicated for the first- or second-line treatment of patients with metastatic carcinoma of the colon or rectum in combination with intravenous 5-fluorouracil-based chemotherapy.
  • Avastin in combination with fluoropyrimidine-irinotecan or fluoropyrimidine-oxaliplatin based chemotherapy is indicated for the second-line treatment of patients with metastatic colorectal cancer who have progressed on a first-line Avastin containing regimen.
  • Avastin is not indicated for adjuvant treatment of colon cancer.

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 (2.4 percent to 0.3 percent). 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.

Severe bleeding: 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, 1.2 percent to 4.6 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.

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 from parts of the body to another part (non-GI fistula formation) was seen in 0.3 percent or less 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 less than one 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 high blood pressure, which was seen in five percent to 18 percent of people, and nervous system and vision disturbances (reversible posterior leukoencephalopathy syndrome), which was seen in less than 0.1 percent 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.

Common side effects that occurred in more than 10 percent 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 percent to 21 percent 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.

First-line Metastatic Colorectal Cancer

In the first-line metastatic colorectal cancer trial, the most common severe to life threatening side effects that increased by two percent or more in people who received Avastin plus IFL chemotherapy vs. IFL alone were weakness (10 percent vs. 7 percent), abdominal pain (8 percent vs. 5 percent), pain (8 percent vs. 5 percent), high blood pressure (12 percent vs. 2 percent), blood clots in the veins of the body (9 percent vs. 5 percent), blood clots inside the abdomen (3 percent vs. 1 percent), a brief loss of consciousness (3 percent vs. 1 percent), diarrhea (34 percent vs. 25 percent), constipation (4 percent vs. 2 percent), reduced white blood cell counts (37 percent vs. 31 percent), and reduced white blood cell counts that may increase the chance of infection (21 percent vs. 14 percent).

Second-line Metastatic Colorectal Cancer

In the second-line metastatic colorectal cancer trial, the most common severe to life threatening and fatal side effects that increased by two percent or more in people who received Avastin plus FOLFOX4 chemotherapy vs. FOLFOX4 alone were diarrhea (18 percent vs. 13 percent), nausea (12 percent vs. 5 percent), vomiting (11 percent vs. 4 percent), dehydration (10 percent vs. 5 percent), blockage of the bowel (4 percent vs. 1 percent), numbness and tingling in fingers and toes (17 percent vs. 9 percent), nervous system disturbances (5 percent vs. 3 percent), tiredness (19 percent vs. 13 percent), abdominal pain (8 percent vs. 5 percent), headache (3 percent vs. 0 percent), high blood pressure (9 percent vs. 2 percent), and severe bleeding (5 percent vs. 1 percent).

Second-line Metastatic Colorectal Cancer in Patients who Have Progressed on an Avastin Containing Regimen in First-line mCRC

In this second-line trial, no new safety signals were observed when Avastin was administered in second-line mCRC patients who progressed on an Avastin containing regimen in first-line mCRC. The safety data was consistent with the known safety profile established in first and second-line mCRC.

For full Prescribing Information and Boxed WARNINGS on Avastin, please visit http://www.avastin.com.

About Genentech

Founded more than 30 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious or life threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.

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Contacts

Genentech
Media Contact:
Holli Dickson, 650-467-6800
or
Advocacy Contact:
Jen Mills, 650-467-6722
or
Investor Contacts:
Thomas Kudsk Larsen, 650-467-2016
Karl Mahler, 011 41 61 687 8503