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

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Abstract

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/m2 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.

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Data Availability

Access to the supporting data for this study will be made available through the Brown University Oncology Research Group (BrUOG) upon request.

Abbreviations

BrUOG:

Brown University Oncology Research Group

HER2+ BC:

Human epidermal growth factor receptor 2—positive breast cancer

NACT:

Neoadjuvant chemotherapy

pCR:

Pathologic complete response

TCHP:

Every 3-week docetaxel, carboplatin, trastuzumab and pertuzumab

wPCbTP:

Weekly paclitaxel and carboplatin with every 3-week trastuzumab and pertuzumab

AC:

Doxorubicin and cyclophosphamide; ddAC: Every 2-week AC with pegfilgrastim

ER-positive/ER-negative:

Estrogen receptor-positive/-negative

TCH:

Every 3-week docetaxel, carboplatin and trastuzumab

FEC-THP:

Fluorouracil, epirubicin and cyclophosphamide followed by docetaxel, trastuzumab and pertuzumab

wP:

Weekly paclitaxel; Cb: Carboplatin; T: Trastuzumab; P: Pertuzumab

AUC:

Area-under-the-curve

CEP17:

Centromeric region of chromosome 17

FISH/CISH:

Fluorescent/chromogenic in situ hybridization

PS:

Performance status

DCIS:

Ductal carcinoma in situ

ANC:

Absolute neutrophil count

T-DM1:

Ado-trastuzumab emtansine

CI:

Confidence interval

RCB:

Residual cancer burden

CR:

Complete response; PR: Partial response

BRCA2:

Breast cancer susceptibility gene 2

HER3:

Human epidermal growth factor receptor 3

BOOG:

Dutch Breast Cancer Research Group

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Acknowledgements

We would like to express our appreciation for the efforts of the staff at the Brown University Oncology Group (BrUOG) administrative office, the research staff at the participating centers, and to all the patients who agreed to participate in the study.

Funding

This research was supported by LifeCycle and the Lura Cook Hull Trust.

Author information

Author notes

  1. J. J. Bian

    Present address: Division of Hematology-Oncology, Maine Medical Center, Portland, ME, USA

  2. S. V. Pandya

    Present address: Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA

Authors and Affiliations

  1. Departments of Medicine and Surgery, Warren Alpert Medical School of Brown University, Lifespan Comprehensive Cancer Centers, Providence, RI, USA

    M. L. Lopresti, J. J. Bian, R. S. Strenger, M. Fenton, S. M. Witherby, D. S. Dizon, C. M. Emmick, T. A. Graves, M. Cutitar & A. J. Olszewski

  2. Department of Obstetrics & Gynecology, Program in Women’s Oncology, Women and Infants Hospital of Rhode Island, Warren Alpert Medical School of Brown University, Providence, RI, USA

    B. J. Sakr, R. D. Legare, S. V. Pandya, A. R. Stuckey, D. A. Edmondson, J. S. Gass & W. M. Sikov

  3. Breast Health Center, 101 Dudley Street, Providence, RI, 02905, USA

    W. M. Sikov

Authors
  1. M. L. Lopresti
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Contributions

All authors contributed to the study conception and design and/or its conduct and analysis. Data analysis was performed by William Sikov, Mary Lopresti and Jessica Bian, with statistical assistance from Adam Olszewski. The first draft of the manuscript was written by William Sikov and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to W. M. Sikov.

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The authors have no disclosures or conflicts of interest related to this manuscript to declare.

Ethical approval

This study was approved by the institutional review boards at all participating hospitals and all patients provided signed informed consent.

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Lopresti, M.L., Bian, J.J., Sakr, B.J. et al. Neoadjuvant weekly paclitaxel and carboplatin with trastuzumab and pertuzumab in HER2-positive breast cancer: a Brown University Oncology Research Group (BrUOG) study. Breast Cancer Res Treat 189, 93–101 (2021). https://doi.org/10.1007/s10549-021-06266-9

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  • DOI: https://doi.org/10.1007/s10549-021-06266-9

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