A new analysis of randomized controlled trials of the widely used new generation cancer drug bevacizumab (marketed by Roche and Genentech as Avastin) found it was linked to an increased risk of deep vein blood clots or venous thromboembolism in the legs or lungs compared with treatments that did not use it.
The research was the work of Dr Shobha Rani Nalluri of Stony Brook University, New York and colleagues and was published in the 19 November issue of the Journal of the American Medical Association, JAMA.
Avastin (bevacizumab) is an angiogenesis inhibitor that works by stopping or slowing down the development of new blood vessels, a process that helps tumors grow and migrate to other parts of the body (metastasis). It is part of a new generation of widely used anti-cancer drugs because it targets a particular process and has shown good results in the treatment of many types of solid cancers such as colorectal cancer, kidney cancer, breast cancer and non-small cell lung cancer (NSCLC).
However, there are concerns that the drug may also raise the risk of venous thromboembolism, a particular cause of illness among cancer patients and one of the leading causes of death. A thromboembolism is where a blood clot develops in a deep vein and then a piece breaks off, travels in the bloodstream to a vessel near the heart and blocks essential bloodflow, causing a heart attack or stroke.
For the study the researchers pooled data from 15 randomized controlled trials covering a total of 7,956 patients with various types of solid cancers in advanced stages.
The analysis showed that:
- 11.9 per cent of patients taking Avastin experienced a venous thromboembolism, and 6.3 per cent had a high grade one.
- Patients on Avastin had a 33 per cent higher risk of developing venous thromboembolism than controls.
- This risk was significantly higher for both all-grade and high grade clots.
- Both high and low doses of Avastin (5 and 2.5 mg per kg per week) were linked to a 31 per cent higher risk of venous thromboembolism.
- The rate of all-grade clots in patients taking Avastin varied depending on the type of cancer.
- The highest shown was in patients with colorectal cancer (19.1 per cent), followed by NSCLC (14.9 per cent), then breast cancer (7.3 per cent) and the lowest was in kidney cancer patients (3.0 per cent).
The authors commented that it is not easy to identify the risk of blood clots with the newer drugs because many of the trials aren’t big enough and thus don’t offer the necessary statistical “power”. By doing this pooled data method (called meta-analysis) one can overcome some of these limitations, and as this study shows, it is now possible to see that there could be a significant risk of deep vein blood clots to patients with solid cancers who take Avastin.
They concluded that:
” The use of bevacizumab was significantly associated with an increased risk of developing venous thromboembolism in cancer patients receiving this drug.”
“The increased risk is observed not only for all-grade venous thromboembolism, but also for clinically significant high-grade venous thromboembolism,” they wrote, adding that:
“This finding will help physicians and patients to recognize the risk of venous thromboembolism with the administration of bevacizumab.”
According to Reuters, a spokesperson for Genentech told the press that the label information for Avastin already bears a warning about blood clots, and it also notes that this has been observed in people who take Avastin and chemotherapy.
Co-author Dr Shenhong Wu, also from Stony Brook University said that the results shouldn’t put cancer patients off taking Avastin but doctors and patients should be more vigilant about signs of blood clots.
“Risk of Venous Thromboembolism With the Angiogenesis Inhibitor Bevacizumab in Cancer Patients: A Meta-analysis.”
Shobha Rani Nalluri; David Chu; Roger Keresztes; Xiaolei Zhu; Shenhong Wu
JAMA, Vol. 300, No. 19, pages 2277-2285, published online November 19, 2008.
Sources: JAMA, Reuters.
Written by: Catharine Paddock, PhD