476 PFS by patient subgroup for standard chemotherapies in combination with bevacizumab (BV) in the first-line treatment of HER2-negative locally recurrent (LR) or metastatic breast cancer (mBC): results from RIBBON-1
Igor BondarenkoJohn A. GlaspyAdam BrufskyO. N. LipatovEA PerezStephenY.T. ChanX.M ZouS. PhanNicholas J. RobertVéronique Dièras
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Tumor angiogenesis, which is necessary for breast cancer growth, invasion and metastases, is regulated by pro-angiogenic factors such as vascular endothelial growth factor (VEGF). Bevacizumab is a recombinant humanized monoclonal antibody that targets VEGF. The addition of bevacizumab to chemotherapy has improved progression-free survival in the first- and second-line treatment of patients with advanced-stage breast cancer. In this article we review the clinical trials testing the utility of bevacizumab for the treatment of metastatic disease.
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As vascular endothelial growth factor (VEGF) plays a central role in tumor growth, invasion and metastasis, inhibiting tumor angiogenesis by blocking the actions of VEGF is a rational therapeutic strategy. Drugs targeting the VEGF system are currently in development and at the most advanced stage of development is bevacizumab. The effect of bevacizumab on breast cancer has been examined in many clinical trials, and promising results have been reported. The clinical effect of bevacizumab monotherapy for breast cancer is not clear; however, the ECOG-E2100 study showed that first-line anti-angiogenic therapy using bevacizumab combined with paclitaxel clearly improved the response for earlier stage metastatic breast cancer (MBC). As a stronger anti-tumor effect is expected when prescribing bevacizumab for patients at an early stage of MBC, many first-line clinical trials using bevacizumab with other combination regimens are currently ongoing. Although the common side effects of bevacizumab are hypertension, proteinuria, wound-healing complications, and thromboembolism, it is a comparatively safe agent. It is expected that the many ongoing clinical trials will establish bevacizumab as a standard first-line therapy for MBC.
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Trastuzumab, other innovative drugs became available, including lapatinib.Therefore, the Dushanbe City Counseling Center, together with the Republican Cancer Institute and the NGO Avesta, recruited the humanitarian drug lapatinib to treat women with metastatic cancer and HER-positive status.A total of 56 women with advanced and metastatic cancer were selected.The primary diagnosis of disseminated breast cancer was in 19 women (34%), and metastatic relapse was in 37 women(66%).CNS metastases were found in 11 women, and liver metastases were found in 26 women.Eleven women (19%) received anthracycline therapy before lapatinib administration.The women were separated by age: 31 women were in the 45-60-year group, and 25 women were in the 60-75 year group.All women received positive IHC and FISH tests to confirm HER-positive status.Results of lapatinib treatment and the drug's effect on metastatic cancer: Women were treated with lapatinib for 24 weeks at a dose of 1,250 mg orally once daily on Days 1-21 continuously in combination with capecitabine.After treatment evaluation, brain metastases had not progressed in 7(12%) women, and two women experienced a decrease in the size of their metastases.8(14%) women with liver metastases had no progression of liver metastases, and 23 women had progression and growth of metastases.Impact of humanitarian delivery of lapatinib on the cancer care system: 1.The Cancer Institute opened a lab to diagnose HER2 status. 2. The Oncology Institute started working on a protocol for the treatment of women with advanced and metastatic cancer, which is vital for a country with limited resources.PO109
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