Bevacizumab (Avastin(R)) Added To Common Chemotherapies Significantly Increases Tumour Shrinkage In HER2-negative Breast Cancer

Main Category: Breast Cancer
Also Included In: Cancer / Oncology
Article Date: 04 Jun 2009 - 0:00 PDT

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Data presented at the American Society of Clinical Oncology (ASCO) 2009 meeting, in Orlando, Florida, show that bevacizumab (Avastin®) plus commonly used chemotherapies increases the chance of the patient living without the disease worsening by up to 36% compared to chemotherapies alone, in women receiving first-line therapy for advanced HER2-negative breast cancer. The Phase III RIBBON-1 study combined bevacizumab with chemotherapies, including capecitabine (Xeloda®), taxanes and anthracyclines and measured progression-free survival (PFS).1 No new safety signals for bevacizumab were observed in the study.

This is the third study (following E2100 and AVADO) to show that bevacizumab can be combined with taxanes for the treatment of advanced breast cancer, and the first to show the benefit of combining bevacizumab with capecitabine or anthracyclines in this group of patients. RIBBON-1 confirms that bevacizumab can be effectively combined with commonly used chemotherapies for first-line treatment of HER- 2 negative metastatic breast cancer, offering patients and physicians more future treatment options. Bevacizumab is not currently licensed for use with anthracyclines or capecitabine and is currently undergoing EMEA review for a licence in combination with docetaxel. It is licensed in combination with paclitaxel for first-line treatment of patients with metastatic breast cancer.

"These results add to the body of evidence showing that adding bevacizumab to a variety of common chemotherapies is able to bring significant benefits to patients. We shouldn't underestimate the importance of telling a breast cancer patient that their disease is stable and that

their tumour has shrunk" said Professor Robert Coleman, Honorary Consultant Medical Oncologist at the Academic Unit of Clinical Oncology, Weston Park Hospital.

Key results from RIBBON-1 included1:

- Up to 36% increase in the chance of the patient living without the disease getting worse.

- A significant increase in tumour shrinkage in all groups of patients that received bevacizumab, with a response rate of up to 51.32%.

- No new safety signals for bevacizumab, confirming the safety and tolerability profile seen in previous studies

Bevacizumab has a well-established tolerability profile and the most frequently observed adverse drug reactions in clinical trials were hypertension, fatigue, neuropathy and proteinuria. The most common side effects are generally manageable, for example, hypertension can generally be managed with conventional antihypertensive treatment.

Breast cancer is now the most common cancer in the UK. There are 45,500 diagnoses of breast cancer each year, with just under 12,000 women around 90 men dying from the disease annually2.

About the RIBBON-1 study

RIBBON-1 is a global double blind, placebo-controlled, randomised phase III trial including 1,237 patients who did not receive previous chemotherapy for their HER 2 negative metastatic breast cancer. The primary objective of RIBBON-1 was to demonstrate superiority in progression-free survival of bevacizumab containing treatment arms compared to the control arms. Bevacizumab yielded superior progression-free survival in both treatment groups. Secondary endpoints for the study included response rate, duration of response, time to treatment failure, overall survival, 1-year survival, safety and tolerability.

RIBBON-1 comprised of two independently powered treatment groups investigating either bevacizumab or placebo in combination with 7 distinct chemotherapy regimens

- Taxanes - docetaxel or protein bound paclitaxel
- Anthracyclines - doxorubicin- or epirubicin-based regimen
Standard anthracyline-based regimens included the following:
- FEC (Fluorouracil (5FU), epirubicin and cyclophosphamide),
- EC (epirubicin and cyclophosphamide),
- AC (doxorubicin and cyclophosphamide),
- FAC (Fluorouracil (5FU), doxorubicin and cyclophosphamide)

- Capecitabine

About Avastin (bevacizumab)

Bevacizumab is the first licensed treatment that inhibits angiogenesis - the growth of a network of blood vessels that supply nutrients and oxygen to cancerous tissues. It targets a naturally occurring protein called VEGF (Vascular Endothelial Growth Factor), a key mediator of angiogenesis, thus choking off the blood supply that is essential for the growth of the tumour and its spread throughout the body (metastasis). Bevacizumab has now demonstrated a progression-free and/or overall survival benefit for patients in four types of metastatic/advanced cancer: colorectal, breast cancer, lung and renal cell cancer.

Roche and Genentech are pursuing a comprehensive clinical programme investigating the use of Bevacizumab in various tumour types (including colorectal, breast, lung, pancreatic cancer, ovarian cancer, renal cell carcinoma and others) and different settings (advanced and adjuvant i.e. post-operation). The total development programme is expected to include over 40,000 patients worldwide.

About Xeloda (capecitabine)

Capecitabine, a targeted oral chemotherapy drug and effective treatment option in the UK for patients with advanced breast cancer since 2002, has been shown to significantly lengthen survival in women with advanced stage disease. Capecitabine is not currently licensed for use with bevacizumab in breast cancer. Its novel mode of action activates the cancer-killing agent 5-FU (5-fluorouracil) directly inside the cancer cells. Furthermore as capecitabine is taken as a tablet, patients can take it in the comfort of their own home, offering them the freedom to carry on with their lives as normally as possible. The most common side effects of capecitabine are hand-foot syndrome (redness and tenderness of the skin) and gastrointestinal side effects (diarrhoea, nausea, vomiting).

References

1. Robert N.J et al. RIBBON 1: Randomised double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for the first line treatment of HER2-negative locally recurrent or metastatic breast cancer. Oral presentation on Monday 1st June ASCO 2009.

2.Cancer Research UK: CancerStats Key Facts on Breast Cancer. Last accessed May 2009

Source
Roche