NCCN VERSION 2 2015

NCCN Guidelines Version 2.2015 Breast Cancer

NCCN Guidelines Index Breast Cancer Table of Contents Discussion

Among other single agents, the Panel includes: cyclophosphamide, carboplatin, docetaxel, albumin-bound paclitaxel, cisplatin, ixabepilone, and epirubicin. Ixabepilone, an epothilone B analogue, is also used for treatment of recurrent or metastatic breast cancer as a single agent. Use of ixabepilone as monotherapy has been evaluated in several phase II trials of women with metastatic breast cancer: in a first-line setting in patients previously treated with anthracycline chemotherapy 469 ; in patients with taxane-resistant metastatic breast cancer 470 ; and in patients with advanced breast cancer resistant to an anthracycline, a taxane, and capecitabine. 471 In the phase II trials, objective response rate, median duration of response, and median OS duration were 41.5% (95% CI, 29.4%–54.4%), 8.2 months (95% CI, 5.7–10.2 months), and 22.0 months (95% CI, 15.6–27.0 months) in the first-line setting; 469 12% (95% CI, 4.7%– 26.5%), 10.4 months, and 7.9 months for the taxane-resistant patients; 470 and 11.5% (95% CI, 6.3%–18.9%), 5.7 months, and 8.6 months for the patients previously treated with an anthracycline, a taxane, and capecitabine. 471 In the study by Perez et al, 471 grade 3/4 treatment-related toxicities included peripheral sensory neuropathy (14%) and neutropenia (54%). Combination Regimens Among combination regimens, the panel includes FAC/CAF; FEC; AC;

doxorubicin; the taxanes, paclitaxel, docetaxel, and albumin-bound paclitaxel; anti-metabolites, capecitabine and gemcitabine; and non-taxane microtubule inhibitors, eribulin, and vinorelbine. Eribulin is a non-taxane microtubule inhibitor used for the treatment of patients with metastatic breast cancer who have previously received at least two chemotherapeutic regimens for the treatment of metastatic disease. Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting. In a phase III trial, 762 patients with metastatic breast cancer were randomized 2:1 to eribulin or treatment of physicians’ choice. One-year OS was 53.9% for patients receiving eribulin versus 43.7% for the control arm, and median OS was 13.12 versus 10.65 months, representing a 19% statistically significant risk reduction ( P = .041). Time to progression was greater with eribulin 3.7 versus 2.2 months for patients in the control arm ( P = .14). 467 Several studies have demonstrated that eribulin is active in metastatic breast cancer. A large randomized trial of heavily pre-treated patients with metastatic breast cancer compared treatment with eribulin versus therapy of physician’s choice. Eribulin demonstrated significant improvement in OS with 2.5-month prolongation of median OS (median for patients treated with eribulin was 13.1 months compared with 10.6 months for those receiving other treatments. HR, 0.81, 95% C,I 0.66- 0.99; P = .041). 467 A phase III trial of eribulin compared with capecitabine in patients with metastatic breast cancer. While a survival advantage was observed with eribulin treatment in all sub-groups of patients, there was a significant survival advantage observed with eribulin over capecitabine among patients with triple-negative breast cancer (15.9 vs 13.5 months; HR 0.838; 95% CI 0.715–0.983; P =.030). 468

EC; CMF; docetaxel, capecitabine; gemcitabine, paclitaxel; gemcitabine, carboplatin; and paclitaxel, bevacizumab.

A series of trials have sought to define the role for bevacizumab, a humanized monoclonal antibody against the vascular endothelial growth factor in the treatment of metastatic breast cancer. The E2100 trial randomized 722 women with recurrent or metastatic breast cancer to first-line chemotherapy with paclitaxel with or without bevacizumab. 472

Version 2.2015, 03/11/15 © National Comprehensive Cancer Network, Inc. 2015, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®. MS-52