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Avastin® (bevacizumab) Plus Interferon Alfa In First-Line Metastatic Kidney Cancer

Avastin is the first medicine approved by the U.S. Food and Drug Administration (FDA) designed to inhibit angiogenesis, a process that connects tumors to the blood supply.1

In July 2009, Avastin was approved for the treatment of people with metastatic renal cell carcinoma in combination with interferon alfa.1 Avastin is designed to specifically block a protein that is a key factor in the growth of most types of cancer. Avastin inhibits this protein known as vascular endothelial growth factor (VEGF), which is produced in elevated amounts in renal cell carcinoma.

The National Comprehensive Cancer Network, an alliance of 21 of the world's leading cancer centers, recommends Avastin in combination with interferon alfa as a treatment for metastatic renal cell carcinoma.2

Renal cell carcinoma is the most common form of kidney cancer and accounts for about nine out of 10 cases.3 According to the American Cancer Society, more than 57,000 people in the United States will be diagnosed with kidney cancer and nearly 13,000 will die from the disease in 2009.4 The number of newly diagnosed cases of renal cell carcinoma has been increasing over the last several decades.5

Avastin in combination with chemotherapy is also approved by the FDA to treat two of the largest causes of cancer deaths — colorectal and lung cancers.1

WARNINGS

  • Gastrointestinal (GI) perforation: Avastin can result in the development of a potentially serious, and sometimes fatal side effect called GI perforation, which is the development of a hole in the stomach, small intestine or large intestine. Symptoms may include abdominal pain, nausea, vomiting, constipation, and fever. Patients must stop Avastin for at least 28 days before voluntary surgery.
  • 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.
  • Severe bleeding: Treatment with Avastin can result in serious and sometimes fatal bleeding. This includes coughing up blood, bleeding in the stomach, vomiting blood, bleeding in the brain, nosebleeds and vaginal bleeding. People who have recently coughed up blood or have serious bleeding should not receive Avastin.

How Avastin Works (Proposed Mechanism Of Action)

  • Avastin is a biologic medicine (not chemotherapy) designed to inhibit the VEGF protein, an important factor in the development and maintenance of blood vessels6
  • VEGF is a potent activator of angiogenesis known to be present throughout the lifecycle of a tumor and is critical to a tumor's ability to grow and spread (metastasize)6

Avastin Clinical Studies In Kidney Cancer

First-Line Treatment In Metastatic Renal Cell Carcinoma

  • In the Phase III study (AVOREN), patients who received Avastin plus interferon alfa had a 67 percent improvement in the time patients lived without their disease worsening (progression-free survival or PFS), compared to those who received interferon alfa alone, which can also be referred to as a 40 percent reduction in the risk of cancer progression or death (HR=0.60, 95 percent CI=0.49, 0.72, p<0.0001)1, 7
    • In AVOREN, one-half of patients who received Avastin plus interferon alfa lived 10.2 months without their disease worsening, compared to 5.4 months for patients who received interferon alfa alone, corresponding to an 89 percent improvement in median PFS.1
    • Median overall survival with Avastin plus interferon alfa was 23 months, a non-significant increase vs. 21 months in the placebo plus interferon alfa (HR=0.86, 95 percent CI=0.72, 1.04, p=0.1291)1, 7
    • Tumor size decreased in 30 percent of patients who received Avastin plus interferon alfa, compared to 12 percent of patients who received interferon alfa alone (p<0.0001)1, 7

Avastin Development Program

  • The Avastin development program is one of the most comprehensive in cancer research since chemotherapy8
  • Avastin is being studied worldwide in more than 450 clinical trials and in approximately 30 different tumor types, including treatment for early-stage cancers8
  • Avastin is also being studied in combination with other targeted medicines without chemotherapy8

Indications

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 is not indicated for adjuvant treatment of colon cancer.1

Avastin is indicated for the first-line treatment of unresectable, locally advanced, recurrent or metastatic non-squamous non-small cell lung cancer in combination with carboplatin and paclitaxel.1

Avastin is indicated for the treatment of metastatic renal cell carcinoma in combination with interferon alfa.1

Important Safety Information and Serious Side Effects

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 (0.3% to 2.4%). 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, the incidence of wound healing complications, including serious and fatal complications, in patients with mCRC who had surgery during the course of Avastin treatment was 15%, and in patients who did not receive Avastin was 4%. 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 5 times more often in people who received Avastin compared to patients who received only chemotherapy. Across cancer types, 1.2% to 4.6% 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 (i.e. requiring medical attention).

  • 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% or less of people. Severe to life threatening stroke or heart problems were seen in 2.6% of people. Too much protein in the urine, which led to kidney problems, was seen in less than 1% 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 5% to 18% of people, and nervous system and vision disturbances (reversible posterior leukoencephalopathy syndrome), which was seen in less than 0.1% of people. Infusion reactions with the first dose of Avastin were uncommon and occurred in less than 3% of people, and severe reactions occurred in 0.2% 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% 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 6 months following the last dose of Avastin.

  • Women should be advised to discontinue nursing or discontinue drug, taking into account the importance of the drug 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 2% or more in people who received Avastin plus IFL (chemotherapy) vs IFL (chemotherapy) alone were weakness (10% vs 7%), abdominal pain (8% vs 5%), pain (8% vs 5%), high blood pressure (12% vs 2%), blood clots in the veins of the body (9% vs 5%), blood clots inside the abdomen (3% vs 1%), a brief loss of consciousness (3% vs 1%), diarrhea (34% vs 25%), constipation (4% vs 2%), reduced white blood cell counts (37% vs 31%), and reduced white blood cell counts that may increase the chance of infection (21% vs 14%).

  • 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 2% or more in people who received Avastin plus FOLFOX4 (chemotherapy) vs FOLFOX4 (chemotherapy) alone were diarrhea (18% vs 13%), nausea (12% vs 5%), vomiting (11% vs 4%), dehydration (10% vs 5%), blockage of the bowel (4% vs 1%), numbness and tingling in fingers and toes (17% vs 9%), nervous system disturbances (5% vs 3%), tiredness (19% vs 13%), abdominal pain (8% vs 5%), headache (3% vs 0%), high blood pressure (9% vs 2%), and severe bleeding (5% vs 1%).

  • 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.

  • Metastatic Kidney Cancer
    In the metastatic kidney cancer trial, the most common severe to fatal side effects that increased by 2% or more in people who received Avastin vs those in the comparison group included tiredness (13% vs 8%), weakness (10% vs 7%), too much protein in the urine (7% vs 0%), high blood pressure (6% vs 1%), and severe bleeding (3% vs 0.3%).

  • Non-small Cell Lung Cancer
    In the non-small cell lung cancer trial, the most common life-threatening to fatal side effects that increased by 2% or more in people who received Avastin vs those in the comparison group were reduced white blood cell counts (27% vs 17%), tiredness (16% vs 13%), high blood pressure (8% vs 0.7%), infection without reduced white blood cell counts (7% vs 3%), blood clots in the veins of the body (5% vs 3%), fever with reduced white blood cell counts (5% vs 2%), inflammation of the lungs (5% vs 3%), infection with severe or life-threatening reduced white blood cell counts (4% vs 2%), low sodium levels in the blood that could lead to seizure or coma.

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

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