NCCN VERSION 2 2015

The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

MS-52

NCCN Guidelines Index

Breast Cancer Table of Contents

Discussion

NCCN Guidelines Version 2.2015

Breast Cancer

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 (

= .041). Time to progression was greater

with eribulin 3.7 versus 2.2 months for patients in the control arm (

.14).

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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;

= .041).

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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).

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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

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; in

patients with taxane-resistant metastatic breast cancer

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; and in

patients with advanced breast cancer resistant to an anthracycline, a

taxane, and capecitabine.

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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;

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12%

(95% CI, 4.7%– 26.5%), 10.4 months, and 7.9 months for the

taxane-resistant patients;

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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,

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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;

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.

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