Frequent Pathologic Complete Responses in Aggressive Stages II to III Breast Cancers With Every-4-Week Carboplatin and Weekly Paclitaxel With or Without Trastuzumab: A Brown University Oncology Group Study William M. Sikov, Don S. Dizon, Rochelle Strenger, Robert D. Legare, Kathy P. Theall, Theresa A. Graves, Jennifer S. Gass, Teresa A. Kennedy, and Mary Anne Fenton From the Departments of Medicine, Surgery, and Obstetrics/Gynecology, The Warren Alpert Medical School of Brown University; and Brown University Oncology Group, Providence, RI. Submitted December 5, 2008; accepted April 2, 2009; published online ahead of print at www.jco.org on August 31, 2009. Supported by Bristol-Myers Squibb, New York, NY, and Genentech, South San Francisco, CA. Presented in part at the 41st Annual Meeting of the American Society of Clinical Oncology, May 13-17, 2005, Orlando, FL; the 28th San Antonio Breast Cancer Symposium, December 8-11, 2005, San Antonio, TX; and the 30th San Antonio Breast Cancer Symposium, December 13-16, 2007, San Antonio, TX. Authors’ disclosures of potential con- flicts of interest and author contribu- tions are found at the end of this article. Corresponding author: William M. Sikov, MD, Department of Medicine, 164 Summit Ave, Providence, RI 02906; e-mail: wsikov@lifespan.org. The Acknowledgment is included in the full-text version of this article, available online at www.jco.org. It is not included in the PDF version (via Adobe® Reader®). © 2009 by American Society of Clinical Oncology 0732-183X/09/2728-4693/$20.00 DOI: 10.1200/JCO.2008.21.4163 A B S T R A C T Purpose To evaluate the efficacy and safety of neoadjuvant carboplatin and weekly paclitaxel  weekly trastuzumab in resectable and locally advanced breast cancer. Patients and Methods Women with stages IIA to IIIB disease received carboplatin dosed by six times the area under the curve every 4 weeks and paclitaxel 80 mg/m 2 weekly for 16 weeks, and weekly trastuzumab was added for human epidermal growth factor receptor 2 (HER2) –positive status. The primary end point was the pathologic complete response (pCR) rate, defined as the absence of invasive disease in the breast and axillary nodes. Postoperative therapies were at the discretion of the treating physicians. Results Fifty-five patients were enrolled, and of these 43 had resectable disease. The median age was 54 years (range, 31 to 74 years). Treatment was well tolerated; there were no episodes of febrile neutropenia or grade 4 thrombocytopenia, and there were only two instances of grade 3 peripheral neuropathy. Overall, the pCR rate was 45%. The pCR rate was 43% (95% CI, 28% to 58%) in patients with resectable disease. Higher pCR rates occurred in patients with HER2-positive tumors (76% v 31% for HER2-negative tumors; P = .003), with estrogen receptor (ER) –negative tumors (75% v 27% for ER-positive tumors; P = .001), or with triple-negative tumors (67% v 12% ER-positive and HER2-negative tumors; P = .002). At a median of 28 months postoperation, recurrence-free survival (RFS) was 88.7%. If patients with ER-positive and HER2-negative tumors are excluded from analysis, patients who achieved a pCR were less likely to experience disease recurrence (RFS, 86%) than those who did not achieve a pCR (RFS, 75%). Conclusion Neoadjuvant carboplatin and weekly paclitaxel  trastuzumab achieve high pCR rates in patients with HER2-positive and triple-negative disease without exposure to an anthracycline. Preliminary RFS results are encouraging but are likely influenced by adjuvant therapy received. Additional study of this regimen in high-risk patients is warranted. J Clin Oncol 27:4693-4700. © 2009 by American Society of Clinical Oncology INTRODUCTION Neoadjuvant chemotherapy (NAC) is standard treat- ment for locally advanced and inflammatory breast cancer, 1 although its role in patients with resectable disease remains unclear. In several randomized studies, NAC failed to improve recurrence-free sur- vival (RFS) and overall survival (OS) compared with identical treatment administered in the postopera- tive setting. 2-4 Still, in retrospective and prospective studies, response to NAC, especially achievement of a pathologic complete response (pCR), is highly predictive of diminished risk of distant disease recurrence. 5-8 This suggests that a treatment regi- men that significantly increases the pCR rate could improve RFS and OS. Although many patients with stages I through III breast cancer receive anthracycline-based adju- vant chemotherapy regimens, such as doxorubicin and cyclophosphamide (AC), there is increasing in- terest in developing effective nonanthracycline regi- mens because of the toxicities of the anthracycline class of agents. Paclitaxel is among the most active single agents in the treatment of metastatic breast JOURNAL OF CLINICAL ONCOLOGY O R I G I N A L R E P O R T VOLUME 27  NUMBER 28  OCTOBER 1 2009 © 2009 by American Society of Clinical Oncology 4693 Downloaded from jco.ascopubs.org on August 12, 2016. For personal use only. No other uses without permission. Copyright © 2009 American Society of Clinical Oncology. All rights reserved.