A total of 722 patients with locally recurrent or metastatic breast cancer were enrolled in the study. Patients were randomised into two treatment groups. One group received the standard treatment, paclitaxel alone and the second group received the new drug combination of paclitaxel with bevacizumab. Researchers found that patients who received bevacizumab in combination with paclitaxel had significantly improved progression free survival of 11.4 months, compared to 6.11 months with paclitaxel alone - a statistically significant difference. Initial overall survival data is also promising and shows a trend towards improved overall survival (28.4 vs 25.2 months) with the new drug combination.
"These results are good news for people with breast cancer," said the study author Dr. R. Zon, Michiana Hematology Oncology, P.C. USA, adding, "A drug with a novel mode of action on the blood vessels within the cancer has not added side effects for patients and those who received the test drugs kept their cancer under control for almost twice as long as patients who received the standard regimen. The next step will be introducing the new drug in patients whose breast cancer has not progressed to metastasis."
The clinical trial was sponsored by the National Cancer Institute (NCI) and conducted by a network of researchers led by the Eastern Cooperative Oncology Group (ECOG), one of the largest clinical cancer research organisations in the U.S. The promising trial results showed only a minimal increase in toxicity when bevacizumab was added to paclitaxel. Manageable side effects of the drug combination included high blood pressure and bleeding.
The antibody drug bevacizumab works by blocking angiogenesis - the formation and growth of new blood vessels - by targeting a protein called vascular endothelial growth factor (VEGF). Cancerous tumours form a network of blood vessels in order to assist their growth, so by blocking the formation of new blood vessels to the tumour it will stop growing and eventually suffocate to death. The drug paclitaxel works by slowing or stopping the division of cancer cells in the body. It affects the cell structures called microtubules, which play an important role in cell function. The combination of the two drugs bevacizumab and paclitaxel enable the cancer cells themselves to be attacked as well as the cancer cell's support system, (the blood vessels that feed the tumour).
Notes: The Eastern Cooperative Oncology Group (ECOG) was established in 1955 as one of the first cooperative groups launched to perform multi-centre cancer clinical trials. The group is a large network of researchers, physicians, and health care professionals at public and private institutions across the US. Funded primarily by the National Cancer Institute (NCI), ECOG is now one of the largest clinical cancer research organisations in the U.S. with almost 6000 physicians, nurses, pharmacists, statisticians, and clinical research associates from the U.S., Canada, and South Africa.
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SS5 Specific issues in metastatic disease
A randomized phase III trial of paclitaxel with or without bevacizumab as first-line therapy for locally recurrent or metastatic breast cancer: Eastern Cooperative Oncology Group trial E2100
R. Zon1, K. Miller2, M. Wang3, J. Gralow4, M. Dickler5, M. Cobleigh6, E. Perez7, T. Shenkier8, N.
1Elkhart General Hospital, Elkhart, USA
2Indiana University Cancer Center, Indianapolis, USA
3Dana Faber Cancer Institute, Boston, USA
4Pudget Sound Oncology Consorttium, Seattle, USA
5Memorial Sloan kettering Cancer Center, New York, USA
6Rush University medical Centre, Chicago, USA
7Mayo Clinic, Jacksonville, USA
8British Columbia Cancer Agency, Vancouver Cancer Center, Vancouver, Canada
9Johns Hopkins Oncology Center, Baltimore, USA
Purpose: Bevacizumab (Avastin®) is a humanized monoclonal antibody that inhibits vascular endothelial growth factor, the key mediator of tumor angiogenesis. Based on evidence of activity in late-stage metastatic breast cancer (MBC), a randomized phase III trial was designed to evaluate the efficacy and safety of combining bevacizumab with paclitaxel as first-line therapy in patients with locally advanced or metastatic breast cancer.
Methods: Patients were randomly assigned to receive paclitaxel 90mg/m2 on days 1, 8 and 15 of a 4-week cycle, either alone or in combination with bevacizumab 10mg/kg on days 1 and 15. The primary endpoint was progression-free survival (PFS); response was assessed by RECIST criteria every 3 cycles. The study had 85% power to detect a 33% improvement in PFS assuming a one-sided type one error of 2.5%, requiring that 650 patients be recruited.
Results: From December 2001 to March 2004, 722 patients were enrolled; 680 patients were eligible. Baseline characteristics were well balanced between the treatment arms. This interim analysis, based on 484 events, shows that combining bevacizumab with paclitaxel significantly improves PFS (11.40 vs 6.11 months; HR = 0.51, p<0.0001) and response rate (29.9% vs 13.8%, p<0.0001) compared to paclitaxel alone. Immature survival data, based on 275 events, shows a trend toward improved overall survival with bevacizumab plus paclitaxel (28.4 vs 25.2 months; HR = 0.84, p=0.12). Bevacizumab plus paclitaxel was generally well tolerated, although there was an increase in selected adverse events with combination therapy; grade 3/4 hypertension ≈16% vs 2% (p<0.0001); grade 3/4 proteinuria 2.0% vs 0% (p=0.002); and grade ¾ bleeding ≈3% vs 0% (p=0.02). The incidence of grade 3/4 thromboembolic events was low in both treatment groups (2% vs 4%). Bevacizumab plus paclitaxel did not compromise quality of life, assessed by FACT-B and FACT-G scores. Conclusions: Bevacizumab plus paclitaxel significantly prolongs PFS compared to paclitaxel in untreated patients with MBC, with a minimal increase in toxicity.