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Breast Cancer Research and Treatment

, Volume 169, Issue 2, pp 333–340 | Cite as

Single-arm, neoadjuvant, phase II trial of pertuzumab and trastuzumab administered concomitantly with weekly paclitaxel followed by 5-fluoruracil, epirubicin, and cyclophosphamide (FEC) for stage I–III HER2-positive breast cancer

  • Julia Foldi
  • Sarah Mougalian
  • Andrea Silber
  • Donald Lannin
  • Brigid Killelea
  • Anees Chagpar
  • Nina Horowitz
  • Courtney Frederick
  • Lawrence Rispoli
  • Trisha Burrello
  • Maysa Abu-Khalaf
  • Kert Sabbath
  • Tara Sanft
  • Debra S. Brandt
  • Erin W. Hofstatter
  • Christos Hatzis
  • Michael P. DiGiovanna
  • Lajos PusztaiEmail author
Clinical trial

Abstract

Purpose

The purpose of this two-cohort Phase II trial was to estimate the pathologic complete response (pCR: ypT0/is ypN0) rate when trastuzumab plus pertuzumab are administered concurrently during both the taxane and anthracycline phases of paclitaxel and 5-fluorouracil/epirubicin/cyclophosphamide (FEC) neoadjuvant chemotherapy.

Methods

The pCR rates were assessed separately in hormone receptor (HR) positive and negative cases following Simon’s two-stage design, aiming to detect a 20% absolute improvement in pCR rates from 50 to 70 and 70 to 90% in the HR-positive and HR-`negative cohorts, respectively.

Results

The HR-negative cohort completed full accrual of 26 patients; pCR rate was 80% (95% CI 60–91%). The HR+ cohort was closed early after 24 patients due to lower than expected pCR rate of 26% (95% CI 13–46%) at interim analysis. Overall, 44% of patients (n = 22/50) experienced grade 3/4 adverse events. The most common were neutropenia (n = 10) and diarrhea (n = 7). There was no symptomatic heart failure, but 28% (n = 14) had ≥ 10% asymptomatic decrease in LVEF; in one patient, LVEF decreased to < 50%. Cardiac functions returned to baseline by the next assessment in 57% (8/14) of cases.

Conclusions

Eighty percent of HR-negative, HER2-positive breast cancers achieve pCR with paclitaxel/FEC neoadjuvant chemotherapy administered concomitantly with pertuzumab and trastuzumab. These results are similar to pCR rates seen in trials using HER2-targeted therapy during the taxane phase only of sequential taxane–anthracycline regimens and suggest that we have reached a therapeutic plateau with HER2-targeted therapies combined with chemotherapy in the neoadjuvant setting.

Keywords

Breast cancer HER-2-positive Trastuzumab Pertuzumab Neoadjuvant therapy Pathological complete response 

Notes

Author contributions

Study design: LP, MD, and CH. Patient accrual: SM, AS, DL, BK, AC, NH, MA-K, KS, TS, DSB, EWH, MD, and LP. Data analysis: CF, TB, JF, LR, LP, and CH. Manuscript writing: JF and LP. Final review of manuscript: all authors.

Funding

Genentech.

Compliance with ethical standards

Conflict of interest

Sarah Mougalian: Consultant/Adviser-Eisai Pharmaceuticals, Hylapharm LLC; Funding-NCCN/Pfizer, Michael DiGiovanna: Renumeration-Dako, Noemarkers (Royalties).

Supplementary material

10549_2017_4653_MOESM1_ESM.doc (66 kb)
Supplementary material 1 (DOC 65 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Julia Foldi
    • 1
  • Sarah Mougalian
    • 1
  • Andrea Silber
    • 1
  • Donald Lannin
    • 1
  • Brigid Killelea
    • 1
  • Anees Chagpar
    • 1
  • Nina Horowitz
    • 1
  • Courtney Frederick
    • 1
  • Lawrence Rispoli
    • 1
  • Trisha Burrello
    • 1
  • Maysa Abu-Khalaf
    • 1
  • Kert Sabbath
    • 1
  • Tara Sanft
    • 1
  • Debra S. Brandt
    • 1
  • Erin W. Hofstatter
    • 1
  • Christos Hatzis
    • 1
  • Michael P. DiGiovanna
    • 1
  • Lajos Pusztai
    • 1
    Email author
  1. 1.Yale Cancer Center, Yale School of MedicineNew HavenUSA

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