Bevacizumab plus neoadjuvant chemotherapy in patients with HER2-negative inflammatory breast cancer (BEVERLY-1)

Claire Rummage, Mercer University College of Pharmacy

According to the American Cancer Society, inflammatory breast cancer (IBC) differs from other types of breast cancer in its symptoms, prognosis, and treatment. The treatment is stated to be chemotherapy to try to shrink the tumor, followed by surgery to remove the cancer, and radiation that follows surgery. Combining these three types of treatment is reported to improve survival. [1]

Inflammatory breast cancer is said to represent the most aggressive presentation of breast cancer and is seen in one to five percent of women in the United States. All women with IBC are recommended to receive a primary systemic regimen consisting of an anthracycline and taxane. [2]

Evidence-based guidelines for the management of IBC are stated to be based on the few clinical trials designed exclusively for IBC. [3]

Bevacizumab plus neoadjuvant chemotherapy in patients with HER2-negative inflammatory breast cancer (BEVERLY-1) [4]
Design Multicenter, single-arm, phase two study; N= 100
Objective To assess the addition of bevacizumab to neoadjuvant and adjuvant chemotherapy in the treatment of patients with human epidermal growth factor receptor two (HER2) negative inflammatory breast cancer
Study Groups N/A
Methods Women with non-metastatic HER2-negative inflammatory breast cancer underwent three week treatment cycles receiving neoadjuvant intravenous fluorouacidl (500mg/m2), epirubicin (100 mg/m2), cyclosphosphamide (500mg/m2), and bevacizumabe (15mg/kg) during cycles 1-4.   Then, they received docetaxel (100mg/m2) and bevacizumab during cycles five through eight. Weeks two through four after surgery patients received adjuvant radiotherapy, hormone therapy (if needed), and adjuvant intravenous bevacizumab.
Duration January 16, 2009 to September 8, 2010
Primary Outcome Measure Pathological complete response in breast and axillary lymph nodes after neoadjuvant treatment
Baseline Characteristics Patients (n= 100)
Age, y 49
Menopause 39%
World Health Organization (WHO) performance status of zero 93%
Ductal pathological type 93%
Hormone receptor positive 63%
HER2 negative 99%
Results Number of pathological complete responses (95% confidence interval) Odds ratio (95% confidence interval) p value
Circulating tumor cells at baseline                                           0.143 0.143
Negative (n= 54) 26% (15-40) 1
Positive (n= 38) 13% (4-23) 2.31 (0.75-7.08)
Circulating tumor cells preoperatively 0.970
Negative (n= 58) 26% (15-39) 1
Positive (n= 7) 0% (0-41) N/A
Adverse Events Common Adverse Events: grade three and four adverse events according to the National Cancer Institute Common Terminology Criteria for Adverse Events: neutropenia (89%), febrile neutropenia (28%), mucositis (23%),
Serious Adverse Events: febrile neutropenia (28%), mucositis (3%), peritonitis (1%), melancholic depression (1%), pyelonephritis (1%), radial fracture (1%)
Percentage that Discontinued due to Adverse Events: 12%
Study Author Conclusions The results suggest that the addition of bevacizumab to neoadjuvant and adjuvant chemotherapy does not provide clinical benefit to patients with non-metastatic HER2-negative inflammatory breast cancer.

These findings show a lack of survival benefit with neoadjuvant bevacizumab in HER2-negative IBC. The main treatment for these patients in the neoadjuvant setting is a taxane-anthracycline-based chemotherapy. Similar to other clinical trials on IBC, a limitation of this study is the small sample size due to the rarity of the disease. Also, the study was non-randomized which can influence the risk for bias. Finally, a short follow up period could prevent the observation of prolonged or remote adverse complications.

 

References

[1] Inflammatory Breast Cancer. American Cancer Society. Available at: http://www.cancer.org/acs/groups/cid/documents/webcontent/002298-pdf.pdf. Last revised June 10, 2015. Accessed April 5, 2016.

 

[2] Dawood S, Merajver SD, Viens P, et al. International expert panel on inflammatory breast cancer: consensus statement for standardized diagnosis and treatment. Annals of Oncology. 2011;22(3):515-523. doi:10.1093/annonc/mdq345.

 

[3] Rea D, Francis A, Hanby AM, et al. Inflammatory breast cancer: time to standardise diagnosis assessment and management, and for the joining of forces to facilitate effective research. British Journal of Cancer. 2015;112(9):1613-1615. doi:10.1038/bjc.2015.115.

 

 

[4]Bertucci F, Fekih M, Autret A, et al. Bevacizumab plus neoadjuvant chemotherapy in patients with HER2-negative inflammatory breast cancer (BEVERLY-1): a multicentre, single-arm, phase 2 study. Lancet Oncol. 2016;

 

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