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Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 2/2018

01-06-2018 | Clinical trial

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

Authors: 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 Pusztai

Published in: Breast Cancer Research and Treatment | Issue 2/2018

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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.
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Metadata
Title
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
Authors
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 Pusztai
Publication date
01-06-2018
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 2/2018
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-017-4653-2

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