Originally published as JCO Early Release 10.1200/JCO.2008.21.4163 on August 31 2009

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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

From the Departments of Medicine, Surgery, and Obstetrics/Gynecology, The Warren Alpert Medical School of Brown University; and Brown University Oncology Group, Providence, RI.

Corresponding author: William M. Sikov, MD, Department of Medicine, 164 Summit Ave, Providence, RI 02906; e-mail: wsikov{at}lifespan.org.

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/m² 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.

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 conflicts of interest and author contributions are found at the end of this article.

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