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Clinical Trial
. 2021 Aug;189(1):93-101.
doi: 10.1007/s10549-021-06266-9. Epub 2021 Jun 4.

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

M L Lopresti  1 , J J Bian  1   2 , B J Sakr  3 , R S Strenger  1 , R D Legare  3 , M Fenton  1 , S M Witherby  1 , D S Dizon  1 , S V Pandya  3   4 , A R Stuckey  3 , D A Edmondson  3 , J S Gass  3 , C M Emmick  1 , T A Graves  1 , M Cutitar  1 , A J Olszewski  1 , W M Sikov  5   6
Affiliations
Clinical Trial

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

M L Lopresti et al. Breast Cancer Res Treat. 2021 Aug.

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.

Keywords: Breast cancer; Carboplatin; Early stage; HER2-positive breast cancer; Neoadjuvant chemotherapy.

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References

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