Neoadjuvant weekly paclitaxel and carboplatin with trastuzumab and pertuzumab in HER2-positive breast cancer: a Brown University Oncology Research Group (BrUOG) study

Purpose In HER2-positive breast cancer (HER2+ BC), neoadjuvant chemotherapy (NACT) with dual HER2-targeted therapy achieves high pathologic complete response (pCR) rates. Anthracycline-free NACT regimens avoid toxicities associated with anthracyclines, but every 3-week TCHP also has substantial side...

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Published in:	Breast cancer research and treatment Vol. 189; no. 1; pp. 93 - 101
Main Authors:	Lopresti, M. L., Bian, J. J., Sakr, B. J., Strenger, R. S., Legare, R. D., Fenton, M., Witherby, S. M., Dizon, D. S., Pandya, S. V., Stuckey, A. R., Edmondson, D. A., Gass, J. S., Emmick, C. M., Graves, T. A., Cutitar, M., Olszewski, A. J., Sikov, W. M.
Format:	Journal Article
Language:	English
Published:	New York Springer US 01-08-2021 Springer Springer Nature B.V
Subjects:	Adjuvant treatment Anthracycline Anthracyclines Antibodies, Monoclonal, Humanized Antineoplastic Combined Chemotherapy Protocols - adverse effects Breast cancer Breast Neoplasms - drug therapy Cancer Cancer research Carboplatin Carboplatin - adverse effects Chemotherapy Clinical Trial Diarrhea Dosage Drug therapy ErbB-2 protein Female Humans Immunotherapy Medicine Medicine & Public Health Monoclonal antibodies Neoadjuvant Therapy Neutropenia Oncology Oncology, Experimental Paclitaxel Paclitaxel - adverse effects Patients Peripheral neuropathy Pertuzumab Receptor, ErbB-2 - genetics Targeted cancer therapy Toxicity Trastuzumab Trastuzumab - adverse effects Universities Neoadjuvant chemotherapy Carboplatin Early stage Breast cancer HER2-positive breast cancer
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Summary:	Purpose In HER2-positive breast cancer (HER2+ BC), neoadjuvant chemotherapy (NACT) with dual HER2-targeted therapy achieves high pathologic complete response (pCR) rates. Anthracycline-free NACT regimens avoid toxicities associated with anthracyclines, but every 3-week TCHP also has substantial side effects. We hypothesized that a weekly regimen might have equivalent efficacy with less toxicity; we also investigated whether poorly responding patients would benefit from switching to AC. Methods Patients with clinical stage II–III HER2+ BC received weekly paclitaxel 80 mg/m 2 and carboplatin AUC2 with every 3-week trastuzumab and pertuzumab (wPCbTP), with the option of splitting the pertuzumab loading dose. After 12 weeks, responding patients continued wPCbTP for another 6 weeks, while non-responders switched to AC. Dose modifications and post-op therapy were at investigator discretion. Results In 30 evaluable patients, the pCR rate was 77% (95% CI 58–90%); 12/14 (86%) in ER-negative and 11/16 (69%) in ER-positive. Only two patients transitioned to AC for non-response, of which one achieved pCR. There were no episodes of febrile neutropenia or grade ≥ 3 peripheral neuropathy, though several patients who continued wPCbTP stopped before week 18. Split-dose pertuzumab was associated with less grade ≥ 2 diarrhea (40%) than the standard loading dose (60%). Conclusion pCR rates with our regimen were as high as reported with TCHP with fewer grade ≥ 3 toxicities, though diarrhea remains a concern. Too few patients had a suboptimal response to adequately test switching to AC. The wPCbTP regimen should be considered an alternative to TCHP as neoadjuvant therapy for HER2+ BC. Trail Registration ClinicalTrials.gov identifier: NCT02789657.
ISSN:	0167-6806 1573-7217
DOI:	10.1007/s10549-021-06266-9