FDA Approves Herceptin For HER2-Positive Metastatic Stomach Cancer

-- First Targeted Medicine Shown to Improve Overall Survival in HER2-Positive Stomach and Gastroesophageal Junction Cancers --

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)-- Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced the U.S. Food and Drug Administration (FDA) has approved Herceptin® (trastuzumab) in combination with chemotherapy (cisplatin plus either capecitabine or 5-fluorouracil [5-FU]) for HER2-positive metastatic (cancer that has spread) cancer of the stomach or gastroesophageal junction, in men and women who have not received prior medicines for their metastatic disease.

People diagnosed with metastatic stomach cancer should have the HER2 status of their tumors determined with FDA-approved diagnostic tests, as only people with HER2-positive disease are eligible for treatment with Herceptin plus chemotherapy.

“Since Herceptin’s approval in HER2-positive advanced breast cancer more than a decade ago, we have continued to study how the HER2 pathway contributes to the growth and spread of other cancers, such as stomach cancer,” said Hal Barron, M.D., executive vice president, Product Development and chief medical officer. “Today’s approval of Herceptin in combination with chemotherapy provides an important new, personalized medicine for people with this life-threatening disease who have few treatment options.”

In January 2010, the European Commission approved Herceptin in combination with chemotherapy for people with metastatic stomach (gastric) cancer with tumors exhibiting high levels of HER2.

About the ToGA study

The FDA approval is based on positive results from an international Phase III study, known as ToGA, which showed that people who received Herceptin plus chemotherapy lived longer compared to those who received chemotherapy alone.

ToGA enrolled 594 people with locally advanced or metastatic, HER2-positive stomach cancer who were randomized to receive Herceptin plus chemotherapy (cisplatin plus either capecitabine or 5-FU) or chemotherapy alone. Results from the final overall survival (OS) analysis demonstrated Herceptin plus chemotherapy improved OS by 37 percent compared to chemotherapy alone (based on HR=0.73, 95 percent CI 0.60-0.91, p=0.0038; median OS 13.5 vs. 11.0 months). An updated OS analysis based on an additional year of follow-up showed a 25 percent improvement in OS (based on HR=0.80, 95 percent CI 0.67-0.97, p=0.02; median OS 13.1 vs. 11.7 months).

In ToGA, the safety profile of Herceptin was consistent with previous studies in HER2-positive breast cancer and no new or unexpected adverse events were seen in the Herceptin plus chemotherapy group (one person in the Herceptin group and two people in the chemotherapy alone group experienced heart failure). Five percent of people in the Herceptin plus chemotherapy group compared to 1.1 percent of people in the chemotherapy alone group had Left Ventricular Ejection Fraction (LVEF) values below 50 percent with a 10 percent absolute decrease in LVEF from pretreatment values. The most common adverse events that were increased with Herceptin and chemotherapy compared to chemotherapy alone were low white blood cell count (78 percent), diarrhea (37 percent) and fatigue (35 percent).

All people in this trial had their tumors tested for HER2 status using two companion diagnostics developed by Dako. Based on HER2 screening results (using both HER2 IHC and FISH diagnostic tests) in ToGA, approximately 22 percent of people with advanced stomach cancer have HER2-positive tumors. A positive result for HER2 overexpression with either test was required for study entry.

About Stomach Cancer

According to the American Cancer Society, an estimated 21,000 Americans will be diagnosed with stomach cancer and more than 10,500 will die from the disease in 2010. More than 64,000 Americans are currently living with the disease. Furthermore, the incidence of cancer in the area where the esophagus and stomach join (gastroesophageal junction) continues to increase. Early diagnosis is challenging because many people do not have symptoms until the disease has advanced into late stages when the tumor cannot be surgically removed or has spread to other parts of the body.

Cancer of the stomach or the gastroesophageal junction can be further divided into categories based on the genetic makeup of the tumor, such as human epidermal growth factor receptor 2 (HER2)-positive and HER2-negative (sometimes referred to as “HER2-normal”). The HER2 testing process, such as scoring and interpretation of results, is different for stomach and breast cancers, which may impact an accurate HER2-positive or HER2-negative diagnosis and treatment.

About Herceptin

Herceptin is a targeted biologic medicine (not a chemotherapy) designed to specifically block the HER2 protein on the surface of some cancer cells. Based on preclinical studies, Herceptin may work by attaching to HER2 receptors to stop signals that make the tumor cells grow and divide, and also by signaling the body’s immune system to destroy the cancerous cells.

Metastatic Gastric Cancer:

Herceptin is approved in combination with the chemotherapy drugs cisplatin, and either capecitabine or 5-fluorouracil, for metastatic HER2-positive stomach cancer or cancer of the gastroesophageal junction, in men and women who have not received prior medicines for their metastatic disease.

Adjuvant Breast Cancer:

Herceptin is approved for the treatment of early-stage breast cancer that is Human Epidermal Growth Factor Receptor 2-positive (HER2+) and has spread into the lymph nodes, or is HER2+ and has not spread into the lymph nodes, but has one high risk feature.* Herceptin can be used in several different ways:

  • As part of a treatment course including the chemotherapy drugs Adriamycin® (doxorubicin), Cytoxan® (cyclophosphamide), and either Taxol® (paclitaxel) or Taxotere® (docetaxel). This treatment course is known as “ACTH
  • With Taxotere and Paraplatin® (carboplatin). This treatment course is known as “TCH
  • Alone after treatment with multiple other therapies, including an anthracycline (Adriamycin)-based therapy (a type of chemotherapy)

*High risk can be defined as ER/PR-negative, tumor size >2 cm, age <35 years, or histological and/or nuclear grade 2 or 3.

Metastatic Breast Cancer:

Herceptin has two approved uses in metastatic breast cancer:

  • Herceptin in combination with the chemotherapy drug Taxol® (paclitaxel) is approved for the first line treatment of Human Epidermal growth factor Receptor 2-positive (HER2+) metastatic breast cancer
  • Herceptin alone is approved for the treatment of HER2+ breast cancer in patients who have received one or more chemotherapy courses for metastatic disease

Important Safety Information

Herceptin treatment can result in heart problems, including those without symptoms (such as reduced heart function) and those with symptoms (such as congestive heart failure). One patient died in an adjuvant (early) breast cancer trial from significantly weakened heart muscle. The risk and seriousness of these heart problems were highest in people who received both Herceptin and a certain type of chemotherapy (anthracycline).

Before taking the first dose of Herceptin and during treatment, a patient’s doctor should check to see if there are any health conditions that may increase the patient’s chance of having serious heart problems. This includes a review of the patient’s health history and tests to see how well the heart muscle is working. These tests may include an echocardiogram or a MUGA scan. Some early breast cancer patients may also need to have a test done after they have finished taking Herceptin to see how well their heart muscle is working.

Some patients have had serious infusion reactions and lung problems; fatal infusion reactions have been reported. These reactions usually occur during or within 24 hours of receiving Herceptin.

The patient’s doctor may need to completely stop Herceptin treatment if the patient has a severe allergic reaction, swelling, lung problems, inflammation of the lung, or severe shortness of breath.

Worsening of low white blood cell counts associated with chemotherapy has also occurred.

Patients must have a HER2 test to determine if their breast or stomach cancer is HER2-positive before using Herceptin, as benefit has only been shown in patients that are HER2-positive.

Herceptin can cause harm to the fetus (unborn baby) when taken by a pregnant woman. This may be due to a lowering of amniotic fluid levels in pregnant women. Women who could become pregnant need to use effective birth control methods during Herceptin treatment and for at least 6 months after treatment with Herceptin.

The most common side effects associated with Herceptin use in breast cancer were fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, shortness of breath, rash, low white and red blood cells, and muscle pain.

The most common side effects associated with Herceptin in combination with chemotherapy use in stomach cancer were low white blood cell counts, diarrhea, fatigue, low red blood cell counts, inflammation of the lining of the mouth, weight loss, upper respiratory tract infections, fever, low platelet counts, swelling of mucus membranes, swelling of the nose and throat, and a change in taste.

Because everyone is different, it is not possible to predict what side effects any one person will have. Patients with questions or concerns about side effects should talk to their doctor.

Patients should read the Herceptin Full Prescribing Information including Boxed WARNINGS, at http://www.herceptin.com.

About Genentech

Founded more than 30 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines for 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.


Krysta Pellegrino, 650-467-6800
Sonali Padhi, 650-467-0842
Diane Schrick, 650-225-1599
Karl Mahler, 011 41 61 687 85 03

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