NCCN VERSION 2 2015

NCCN Guidelines Version 2.2015 Breast Cancer

NCCN Guidelines Index Breast Cancer Table of Contents Discussion

This trial documented superior PFS (11.8 months vs. 5.9 months; HR 0.60; P <.001) favoring bevacizumab plus paclitaxel compared with paclitaxel alone. A similar trial enrolled 736 patients who were randomized to treatment with docetaxel and bevacizumab or docetaxel and placebo. 473 This trial also documented increased PFS in the arm containing bevacizumab (10.1 months vs. 8.2 months with docetaxel alone; HR 0.77; P =.006). An additional trial, RIBBON-1, combined bevacizumab with capecitabine, with a taxane (docetaxel, nab-paclitaxel), with anthracyclines (FEC, CAF, AC, or EC), or with the same chemotherapy alone. Results of this trial show a statistically significant increase in PFS with bevacizumab and capecitabine (8.6 months vs. 5.7 months; HR 0.69; P < .001); and taxane- or anthracycline- (9.2 months vs. 8.0 months; HR 0.64; P <.001) containing arms. 474,475 None of these studies demonstrate an increase in OS or quality of life when analyzed alone or in a meta-analysis combining the trials. 476 The increase in PFS with bevacizumab is modest, and appears the greatest in combination with paclitaxel, especially as reported in an unpublished analysis provided to the FDA. 477 As with endocrine therapy, sequential responses are often observed with chemotherapy, supporting the use of sequential single agents and combination chemotherapy regimens. The current guidelines include doses and schedules of these single agents and combination regimens for metastatic breast cancer. Failure to achieve a tumor response to 3 sequential chemotherapy regimens or ECOG performance status of 3 or greater is an indication for supportive therapy only. In this context, failure to respond to a chemotherapy regimen means the absence of even a marginal response to the use of a given chemotherapy regimen. Response to a chemotherapy regimen followed by progression of disease is not considered a failure to experience response.

Patients with metastatic breast cancer frequently develop many anatomically localized problems that may benefit from local irradiation, surgery, or regional chemotherapy (eg, intrathecal methotrexate for leptomeningeal carcinomatosis). HER2-Targeted Therapy for Stage IV or Recurrent Metastatic Disease Patients with tumors that are HER2-positive may derive benefit from treatment with HER2 targeted therapy. The panel recommends selecting patients for HER2-targeted therapy if their tumors are either positive for HER2 by ISH or 3+ by IHC. HER2 testing recommendations are described in the guideline. Patients with tumors IHC 0 or 1+ for HER2 or ISH not amplified have very low rates of HER2-targeted response, and HER2 targeted therapy. 478 Adequate standardization and validation of HER2 assays by ISH and IHC used in clinical practice is a concern, and data suggest that false-positive determinations are common. 20,21,479-481 Recommendations regarding HER2 testing have been published. 479,481 The NCCN Panel has categorized HER2 targeting regimens as either preferred or other. Preferred First-Line Regimens A randomized, double-blind, phase III study compared the efficacy and safety of pertuzumab in combination with trastuzumab and docetaxel versus trastuzumab and docetaxel as first-line treatment for HER2-positive metastatic breast cancer. 482 The primary endpoint of the study was independent assessment of PFS. The secondary endpoints were PFS assessed by investigator, objective response rate, OS, and safety. A total of 808 patients were enrolled in this trial. 482 The addition of pertuzumab provided a statistically significant improvement in PFS First-Line Regimens for HER2-Positive Tumors

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-53