NCCN VERSION 2 2015

NCCN Guidelines Version 2.2015 Breast Cancer

NCCN Guidelines Index Breast Cancer Table of Contents Discussion

pertuzumab, trastuzumab, and docetaxel. pCR is defined by the FDA as “the absence of invasive cancer in the breast and lymph nodes.” In the NeoSphere trial, 417 patients were randomized 1:1:1:1 to receive trastuzumab plus docetaxel, or pertuzumab and trastuzumab plus docetaxel, or pertuzumab and trastuzumab, or pertuzumab plus docetaxel. Forty-five point eight percent [95% CI, 36.1–55.7] of patients who received pertuzumab plus trastuzumab and docetaxel achieved pCR, compared with only 29% [CI, 20.6–38.5] of patients who achieved pCR on the trastuzumab plus docetaxel regimen ( P = .0063). 169 The TRYPHAENA was a phase II, randomized, multicenter trial designed to evaluate the safety and tolerability of trastuzumab and pertuzumab in combination with anthracycline-, or carboplatin-based neoadjuvant chemotherapy. A total of 225 patients with HER2-positive, locally advanced (T2-3, N2-3, M0; T4a-c, any N,M0), inflammatory (T4d, any N,M0), or early-stage breast cancer (tumors >2 cm) were enrolled and randomized 1:1:1 to receive 6 cycles of neoadjuvant therapy with FEC plus trastuzumab and pertuzumab followed by docetaxel, trastuzumab, and pertuzumab; or FEC followed by docetaxel, trastuzumab, and pertuzumab; or docetaxel, carboplatin, and trastuzumab along with pertuzumab. Based on the assessment of pCR, all 3 regimens seem active. The reported pCR ranged from 57.3% to 66.2%. The highest pCR was observed in patients who received pertuzumab, trastuzumab, docetaxel, and carboplatin chemotherapy, with a pCR of 66.2%. The adverse events reported in the trial were consistent with what was observed which each of the three agents, and low rates of symptomatic left ventricular systolic dysfunction were reported. The NCCN Panel has included pertuzumab-based regimens as neoadjuvant therapy options for patients with early-stage (≥T2 or ≥N1), HER2-positive tumors.

Several randomized trials have assessed the value of neoadjuvant endocrine therapy in postmenopausal women with ER-positive breast cancer. These studies have generally compared the rates of objective response and rates of breast-conserving surgery among treatment with tamoxifen, anastrozole, anastrozole plus tamoxifen, or letrozole. These studies consistently demonstrate that the use of either anastrozole or letrozole alone provides superior rates of breast-conserving surgery and usually objective response when compared with tamoxifen. 170,171 Based on these trials, if preoperative endocrine therapy is to be utilized, an aromatase inhibitor is preferred in the treatment of postmenopausal women with hormone receptor-positive disease. Local therapy following a complete or partial response to preoperative systemic therapy is usually lumpectomy if possible along with surgical axillary staging. If lumpectomy is not possible or progressive disease is confirmed, mastectomy is performed along with surgical axillary staging with or without breast reconstruction. Surgical axillary staging may include SLN biopsy or level I/II dissection. If SLN biopsy was performed before administering preoperative systemic therapy and the findings were negative, then further ALN staging is not necessary. If an SLN procedure was performed before administering preoperative systemic therapy and the findings were positive, then a level I/II ALN dissection should be performed. If an inoperable tumor fails to respond, or if the response is minimal, after several cycles of preoperative systemic therapy, or the disease progresses at any point, an alternative chemotherapy regimen and/or preoperative radiation therapy should be considered followed by local therapy, usually a mastectomy plus axillary dissection, with or without breast reconstruction.

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-19