Bevacizumab In Combination With Commonly Used Chemotherapies Improves Progression-Free Survival In Women With Previously Treated Advanced Breast Cancer

Results from the RIBBON 2 study presented at the 32nd Annual San Antonio Breast Cancer Symposium in December 2009 suggest a potential new role for bevacizumab as second-line treatment in advanced breast cancer.(1)

Despite the treatment improvements that have already been made, breast cancer continues to be the leading cause of cancer death in women under the age of 55. More than one million women are diagnosed with breast cancer each year, leading to over 500,000 deaths from the disease worldwide.(2, 3)
Bevacizumab is an antibody that specifically binds and blocks the biological effects of VEGF (vascular endothelial growth factor), a key driver of tumour angiogenesis. Bevacizumab’s precise mode of action allows it to be combined effectively with a broad range of chemotherapies and other anti-cancer treatments. Already approved for the first-line treatment of patients with advanced breast cancer in combination with paclitaxel, bevacizumab had its European license recently extended to allow combination with docetaxel.
Study Design
RIBBON 2 is an international, multicentre, randomised, doubleblind, placebo-controlled clinical study that enrolled 684 patients with previously treated metastatic HER2-negative breast cancer. The trial evaluated the combination of either bevacizumab or placebo with an investigator’s choice of chemotherapy. Bevacizumab was administered every two or three weeks until disease progression. The following chemotherapy regimens were used in the study:
• Taxanes: paclitaxel, protein-bound paclitaxel or docetaxel
• Gemcitabine
• Capecitabine
• Vinorelbine
The primary endpoint of the study was progression-free survival (PFS). PFS was defined as the time from randomisation to disease progression or death.
Secondary endpoints included objective response rate, one-year survival rate, overall survival, PFS assessment by chemotherapy type and safety.
In Combination With Commonly Used Chemotherapies, Bevacizumab Improves Progression-Free Survival By 28%
The study met its primary endpoint of showing a statistically significant and clinically meaningful improvement in PFS with the combination of bevacizumab with commonly used secondline chemotherapy.
Key results from RIBBON 2 are:
• A 28% improvement in progression-free survival (Hazard Ratio= 0.78, p=0.0072).
• Women who received bevacizumab plus chemotherapy had a median PFS of 7.2 months compared to 5.1months for those who received chemotherapy alone.
• The observed increase in tumour shrinkage in patients that received bevacizumab (response rate = 39.5% vs. 29.6% for bevacizumab + chemotherapy vs. chemotherapy alone) further supports the activity of bevacizumab in this setting (p=0.0193).
Adverse events were consistent with those previously reported for bevacizumab and no new bevacizumab safety findings were observed in the study.
Conclusion
RIBBON 2 is another positive phase III trial, adding to the clinical evidence for bevacizumab as a treatment for women with advanced breast cancer, this time in the second-line setting. This is a significant result as most women with advanced disease will see their cancer get worse when their initial chemotherapy stops working, and currently the only option for these women is subsequent chemotherapy.
Dr Adam Brufsky, M.D., Medical Director of the Women’s Cancer Center, University of Pittsburgh Medical Center and principal investigator of the study commented: “This is the first phase III study to show that the combination of an anti-angiogenic medicine with commonly used second-line chemotherapy can extend the time women with advanced breast cancer live without the disease worsening.”
Bevacizumab has proven survival benefits across several types of cancer. In Europe, Avastin is approved for the treatment of the advanced stages of four common types of cancer: Colorectal cancer, breast cancer, non-small cell lung cancer (NSCLC) and kidney cancer. It is anticipated that an application will shortly be submitted to the European Medicines Agency to update the licence for Avastin to reflect the use of bevacizumab in women with previously treated advanced breast cancer.
References: 1- Brufsky A. RIBBON-2: A Randomized, Double- Blind, Placebo-Controlled, Phase III Trial Evaluating The Efficacy And Safety Of Bevacizumab In Combination With Chemotherapy For Second-Line Treatment Of HER2-Negative Metastatic Breast Cancer. Presented at the 32nd CTRC-AACR San Antonio Breast Cancer Symposium. December 9-13, 2009. San Antonio, TX. Abstract 42.
2- Boyle P et al. World Cancer Report 2008 IARCPress, Lyon, 2008.
3- Ferlay J et al. GLOBOCAN 2002: Cancer Incidence, Mortality
and Prevalence Worldwide IARC CancerBase No. 5. version 2.0, IARCPress, Lyon, 2004.
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