P2-18-04: Pilot Evaluation of Bevacizumab (Bev) in Combination with Docetaxel (T) and Cyclophosphamide (C) as Adjuvant Treatment (AdjRx) for Patients (pts) with Early Stage (ES) Breast Cancer (BrCa).
Authors: Gullo G , Kennedy J , Breathnach O , McCaffrey J , Keane M , Martín M , Gupta R , Leonard G , Tryfonopoulos D , O'Shea T , Crown J 
Published: June 2012

Abstract
Background
The combination of Bev + chemotherapy (CRx) has been shown to produce superior response rates and progression free survival compared to CRx alone, providing a rationale for the study of Bev with AdjCRx for pts with ESBrCa. As Bev can cause hypertension (HTN) and may increase the risk of cardiac failure, there is a rationale for studying a standard non-anthracycline (Anth) AdjCRx with Bev, e.g. TC (docetaxel-cyclophosphamide). We performed a pilot phase II study to evaluate the feasibility and toxicity of TC+Bev in pts with ESBrCa in preparation for participation in a random assignment trial. We have previously reported preliminary toxicity data.
Methods: Eligibility criteria included: ESBrCa which was HER-2 normal, node+ or, N- and primary tumour (T) &gt;2 cm and receptor negative, or T &gt;3 cm, normal left ventricle ejection fraction (LVEF), no active/uncontrolled cardiovascular disease, normal organ and marrow function. Treatment consisted of four 3-weekly cycles of docetaxel 75 mg/m2 together with cyclophosphamide 600 mg/m2. Patients commenced Bev 15 mg/kg i.v. on day 1, and then every 3 weeks to a total of 18 cycles of treatments. Pts were monitored clinically, with echocardiograms and with serial estimations of BNP and troponin.
Results: A total of 106 female pts were accrued in 9 ICORG sites between 11/2008 and 7/2010. Ages ranged from 25–75 (median 52). On 20/06/2011, 105 pts have completed study Rx, 1 will finish 7/2011. A total of 36 serious adverse events (SAEs) have been reported so far, 33 involving hospital admission, 3 serious for other reasons. In 25 (24%) pts study Rx was discontinued due to: HTN-9, intestinal perforation-2, consent withdrawl-7, infection-2, proteinuria-1, anaphylaxis-1, cancer relapse-1, arthralgia-1, anal fistula-1. The two perforations occurred at cycles 1 and 16 of Bev respectively. Neither pt with perforation had history of prior abdominal surgery. The median number of cycles achieved by the discontinued pts was 9. HTN of any grade occurred in 49 out of 103 (48%) pts who had no HTN at baseline (BL) and 42 of them required Rx. Among pts who experienced HTN on study Rx and completed Bev, 34 (81%) were still on anti-hypertensive 4 weeks after last infusion of Bev. Forty-one (39%) pts had LVEF drop &gt;10% from BL during study Rx. In 8 (7.5%) pts LVEF declined below 50%, 6 are documented to have recovered to normal, 2 had no further LVEF measurements (1 declined, 1 unknown reason). No episodes of CCF were reported. Troponin and BNP levels were normal in all 57 pts with serial measurements. Fourteen pts required treatment for neutropenia-related infection or for abscess/fistula.
Conclusions: In this study Bev overall toxicity in ESBC pts was similar to that reported for pts with MBC, and Bev discontinuation due to toxicity was relatively frequent. Although no pt developed CCF 7.5% of decline in LVEF&lt;50% was observed. Intestinal perforation can occur in ESBC pts in absence of prior intestinal surgery and in the post-CRx phase of Bev. Pts receiving Bev with non-Anth AdjCRx require careful monitoring for toxicity.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-18-04.