Herceptin delivers improvement in disease-free survival for women with early-stage HER2-positive breast cancer

Main Category: Breast Cancer
Article Date: 16 May 2005 - 12:00 PDT

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Roche and Breast International Group (BIG)1 announced that targeted anti-cancer therapy Herceptin (trastuzumab) achieved a highly significant 46% reduction in the risk of cancer coming back for women with early-stage HER2-positive breast cancer. HERA (HERceptin Adjuvant), an international, phase III study, investigated treatment with Herceptin for 12 or 24 months versus no treatment (observation) in patients who had previously undergone a range of surgical, chemotherapy and /or radiotherapy interventions. HER2-positive breast cancer is a particularly aggressive form of the disease which affects approximately 20 - 30% of women with breast cancer2, so early and accurate determination of HER2 status is an essential step in the management of the disease.

Dr Martine Piccart, Head of the Medicine Department at the Jules Bordet Institute in Brussels and lead investigator of the HERA study, commented, "In the advanced breast cancer setting, Herceptin has already demonstrated that it prolongs patients' lives. To see such impressive results with Herceptin in early-stage breast cancer, already at the interim analysis, is a major breakthrough in the treatment of this aggressive disease. These results now add to the growing body of evidence that Herceptin should be considered the foundation of care for HER2-positive breast cancer patients, regardless of the stage of their disease."

HERA's one-year follow-up results were highlighted for the first time at a press briefing organised by the American Society of Clinical Oncology (ASCO). Also highlighted at the briefing was a joint interim analysis of two North American trials which similarly provided remarkable results for Herceptin in early-stage HER2-positive breast cancer. This data showed that Herceptin in combination with a particular chemotherapy regimen [1] provided:

-- a 52% reduction in the risk of cancer coming back, and;

-- a 33% reduction in the risk of death.

Speaking about her experience with Herceptin treatment, as a HERA study participant in the UK, Sharron Beesley said: "When I was first diagnosed, my doctor told me I had an aggressive form of the breast cancer, called HER2-positive. It was very frightening, but I was relieved to learn about the HERA trial, studying a treatment specifically for my type of breast cancer. Through the trial, I have been on Herceptin and compared to my initial treatment with chemotherapy, my quality of life with Herceptin has been great - I haven't experienced any major side effects and I have been able to continue my lifestyle just as before. Best of all, I feel good and I am still cancer free - the doctor says there is even a good chance my cancer won't come back."

Roche will now work closely with health authorities around the world to make Herceptin accessible to patients with early-stage HER2-positive breast cancer as quickly as possible.

About the HERA study

HERA, conducted by Roche and BIG, was one of the largest studies ever carried out among breast cancer patients; enrolment to the trial began in December 2001, and nearly 5,100 HER2-positive patients have been enrolled at 480 sites in 39 countries across the world. HERA is a randomised trial which evaluates the use of standard adjuvant systemic chemotherapy and radiotherapy (if applicable) followed with or without Herceptin every three weeks for 12 or 24 months in women with early-stage HER2-positive breast cancer. The HERA study allowed for the use of a wide range of chemotherapy regimens, and both lymph node-positive and lymph node-negative patients were eligible for entry into the trial.

According to the interim analysis, the primary efficacy endpoint had been met, showing that in both 12- and 24-month arms, patients who received Herceptin had statistically significant improvement in disease-free survival (the length of time after treatment during which no disease is found). At the one- year follow up, the secondary endpoint of overall survival had not yet been reached, but an improvement in overall survival is also possible as the data mature.

The interim analysis compared Herceptin versus observation and did not include a comparison of 12 months versus 24 months. The trial will continue to assess this comparison and data will become available in due time as the study matures.

The HERA study has an external Independent Data Monitoring Committee (IDMC) that regularly reviews safety data. No safety concerns were raised by the IDMC, and the incidence of congestive heart failure was very low (0.5% in the Herceptin arms vs. 0% in the observation arm). Patients in this study will continue to be followed for any side effects.

About the NSABP and NCCTG studies

The two studies were sponsored by the National Cancer Institute, part of the National Institutes of Health, and conducted by a network of researchers led by the National Surgical Adjuvant Breast and Bowel Project (NSABP) and the North Central Cancer Treatment Group (NCCTG), who conducted a prospectively-designed joint interim analysis. The NCCTG study enrolled its first patient in June 2000 and has enrolled 3,406 patients; the NSABP study began enrolment in March 2000 and has enrolled 2,085 patients. The joint interim analysis was based on information from 3,300 patients. These studies have now stopped enrolling new patients and the cooperative groups will continue to monitor patients for longer-term data. Each of the studies was a randomised, controlled trial that evaluated the combination of doxorubicin and cyclophosphamide (AC) followed by paclitaxel, with or without Herceptin using different treatment schedules of paclitaxel in women with early stage HER2-positive breast cancer.

Each of these studies has an independent, external Data Monitoring Committee (DMC) that reviewed data from the studies, including cardiac safety data. There was three to four percent more incidence of congestive heart failure in patients receiving the combination of Herceptin plus chemotherapy. Patients in this study will continue to be followed for any additional side effects.

About breast cancer and Herceptin

Eight to nine percent of women will develop breast cancer during their lifetime, making it one of the most common types of cancer in women.3 Each year more than one million new cases of breast cancer are diagnosed worldwide, with a death rate of nearly 400,000 people per year.

In HER2-positive breast cancer, increased quantities of the HER2 protein are present on the surface of the tumour cells. This is known as 'HER2 positivity.' High levels of HER2 are present in a particularly aggressive form of the disease which responds poorly to chemotherapy. Research shows that HER2-positivity affects approximately 20-30% of women with breast cancer.

Herceptin is a humanised antibody, designed to target and block the function of HER2, a protein produced by a specific gene with cancer-causing potential. Herceptin has demonstrated improved survival in the advanced (metastatic) setting, where its addition to chemotherapy allows patients to live up to one-third longer than chemotherapy alone. Herceptin received approval in the European Union in 2000 for use in patients with metastatic breast cancer, whose tumours overexpress the HER2 protein, as first-line therapy in combination with paclitaxel where anthracyclines are unsuitable, and as a single agent in second- and third-line therapy. In 2004, it also received approval for use in combination with docetaxel as a first-line therapy in HER2-positive patients who have not received chemotherapy for their metastatic disease. Herceptin is marketed in the United States by Genentech, in Japan by Chugai and internationally by Roche. Since 1998, Herceptin has been used to treat over 230,000 HER2-positive breast cancer patients worldwide.

About Roche

Headquartered in Basel, Switzerland, Roche is one of the world's leading research-focused healthcare groups in the fields of pharmaceuticals and diagnostics. As a supplier of innovative products and services for the early detection, prevention, diagnosis and treatment of disease, the Group contributes on a broad range of fronts to improving people's health and quality of life. Roche is a world leader in diagnostics, the leading supplier of medicines for cancer and transplantation and a market leader in virology. In 2004 sales by the Pharmaceuticals Division totalled 21.7 billion Swiss francs, while the Diagnostics Division posted sales of 7.8 billion Swiss francs. Roche employs roughly 65,000 people in 150 countries and has R&D agreements and strategic alliances with numerous partners, including majority ownership interests in Genentech and Chugai. Additional information about the Roche Group is available on the Internet (http://www.roche.com). All trademarks used or mentioned in this release are legally protected.

Further information:
- Herceptin http://www.HER2status.com and http://www.heratrial.com
- Genentech: http://www.gene.com
- Roche in Oncology

Roche contact:
Holly Kania
Associate International Communications Manager
Telephone: +41 (0)61 688 3773
Email: holly.kania@roche.com

References:
1. Collaborative partners for the HERA study include: Roche, the Breast International Group (BIG) and its affiliated collaborative groups, plus non-affiliated collaborative groups, and independent sites
2. Harries M, Smith I. The development and clinical use of trastuzumab (Herceptin). Endocr Relat Cancer 9: 75-85, 2002.
3. World Health Organization, 2000

SOURCE: Ketchum