Study To Evaluate the Efficacy and Safety Of Bevacizumab, and Associated Biomarkers, In Combination With Paclitaxel Compared With Paclitaxel Plus Placebo as First-line Treatment Of Patients With Her2-Negative Metastatic Breast Cancer

This is a Phase III, randomized, double-blind, placebo-controlled multicenter study to evaluate the efficacy and safety of bevacizumab administered in combination with paclitaxel in patients with previously untreated, locally recurrent, or metastatic HER2-negative breast cancer. Patients will be randomized to one of two treatment arms: bevacizumab or placebo. All patients will be given an intravenous (IV) infusion of of paclitaxel (90 mg/m2) for 3 weeks during each 28-day cycle. bevacizumab or placebo (10 mg/kg) will be administered by IV infusion on Days 1 and 15 of each 28-day cycle. Patients will be treated until disease progression, unacceptable toxicity or death from any cause occurs.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

* Histologically or cytologically confirmed, HER2-negative adenocarcinoma of the breast, with measurable or non-measurable locally recurrent or metastatic disease. Locally recurrent disease must not be amenable to resection with curative intent.
* ECOG performance status of 0 or 1
* For women of childbearing potential, use of an acceptable and effective method of non-hormonal contraception
* For patients who have received recent radiotherapy, recovery prior to randomization from any significant acute toxicity, and radiation treatments have to be completed more than 3 weeks from randomization

Exclusion Criteria:

Disease-Specific Exclusions:

* HER2-positive status
* Prior chemotherapy for locally recurrent or metastatic disease
* Prior hormonal therapy \< 2 weeks prior to randomization
* Prior adjuvant or neo-adjuvant chemotherapy is allowed, provided its conclusion has been for at least 12 months prior to randomization
* Investigational therapy within 28 days of randomization

General Medical Exclusions:

* Life expectancy of \< 12 weeks
* Inadequate organ function
* Uncontrolled serious medical or psychiatric illness
* Active infection requiring intravenous (IV) antibiotics at screening
* Pregnancy or lactation
* History of other malignancies within 5 years prior to screening, except for tumors with a negligible risk for metastasis or death

• DERIVEDMasuda N, Takahashi M, Nakagami K, Okumura Y, Nakayama T, Sato N, Kanatani K, Tajima K, Kashiwaba M. First-line bevacizumab plus paclitaxel in Japanese patients with HER2-negative metastatic breast cancer: subgroup results from the randomized Phase III MERiDiAN trial. Jpn J Clin Oncol. 2017 May 1;47(5):385-392. doi: 10.1093/jjco/hyx001. PMID 28158579
• DERIVEDMiles D, Cameron D, Bondarenko I, Manzyuk L, Alcedo JC, Lopez RI, Im SA, Canon JL, Shparyk Y, Yardley DA, Masuda N, Ro J, Denduluri N, Hubeaux S, Quah C, Bais C, O'Shaughnessy J. Bevacizumab plus paclitaxel versus placebo plus paclitaxel as first-line therapy for HER2-negative metastatic breast cancer (MERiDiAN): A double-blind placebo-controlled randomised phase III trial with prospective biomarker evaluation. Eur J Cancer. 2017 Jan;70:146-155. doi: 10.1016/j.ejca.2016.09.024. Epub 2016 Nov 4. PMID 27817944