Abstract P5-10-17: Bevacizumab (Bev) in Combination with Docetaxel (T) and Cyclophosphamide (C) as Adjuvant Treatment (AdjRx) for Patients (pts) with Early Stage (ES) Breast Cancer (BrCa) and Normal HER-2 Status. A Pilot Evaluation
Authors: Crown JP , Gullo G , Tryfonopoulos D , Keane M , Breathnach O , McCaffrey J , Martin MJ , Gupta R , Leonard G , Fennelly D , Kennedy JM. 
Published: April 2011

Abstract
In random assignment trials, the combination of Bev+ chemotherapy has been shown to produce superior response rates and progression free survival compared to chemotherapy alone, providing a rationale for the study of Bev in the AdjRx of pts with ESBrCa. As a principal side effect of Bev is hypertension (HTN), anthracycline-containing (Anth) AdjRx may pose additional cardiovascular risks. The role of Anth in Her2 normal ESBC is uncertain. TC is a standard non-Anth AdjRx. We performed a single arm pilot study to evaluate the feasibility and toxicity of TC+Bev in pts with ESBC in preparation for participation in a random assignment trial. Methods: Eligibility criteria included: ESBC which was HER-2 normal, node-positive or &gt;2 cm and receptor negative, or &gt;3 cm and receptor positive, normal cardiac ejection fraction (EF), no active or 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 bevacizumab 15 mg/kg i.v. on day 1, and q 3 weeks to a total of 19 treatments. Pts were monitored clinically, with echocardiograms and with serial estimations of BNP and troponin.
Results: A total of 105 female pts were accrued in 9 ICORG sites between Dec 2008 and June 2010. Ages ranged from 26-86 (median 55). At June 2010, 33 have completed all phases of therapy, 54 are still on treatment. Eighteen pts have been removed from study due to: HTN -7, intestinal perforation -2, withdrew consent-4, proteinuia-1, anaphylaxis-1, infection-3. The perforations occurred at cycles 9 and 19. Neither pt. with perforation had prior abdominal surgery. The median number of cycles achieved by the discontinued pts was 9. HTN requiring Rx occurred in 25 pts. Among 12 with HTN who have completed Bev, 2 are off HTN meds, and 9 are on reducing doses. The median EF at base line was 67%, at 13 cycles (42 pts) 63%, 18 cycles (27 pts) 66%. Six pts had EF drop &gt;10%, in 3 of these EF fell below 50% as last recorded value. There were no episodes of clinical cardiac failure. Troponin and BNP levels were normal in all 57 pts with serial measurements. Thirteen pts required treatment for neutropenia-related infection or for abscess.
Conclusions: The spectrum and frequency of bevacizumab toxicity in our population of healthy adjuvant pts is similar to that reported for pts with metastatic BC and other malignancies. Hypertension is the principal cause of treatment discontinuation, but cardiac toxicity appears to be limited, with this non-anth chemotherapy +Bev. Intestinal perforation can also occur in pts with ESBC. These toxicities can occur in the post chemotherapy phase of Bev therapy. Pts enrolled on random assignment trials of Bev containing AdjRx require careful monitoring for toxicity.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-10-17.