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
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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.
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.
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.
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.
KeywordsBreast cancer HER-2-positive Trastuzumab Pertuzumab Neoadjuvant therapy Pathological complete response
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.
Compliance with ethical standards
Conflict of interest
Sarah Mougalian: Consultant/Adviser-Eisai Pharmaceuticals, Hylapharm LLC; Funding-NCCN/Pfizer, Michael DiGiovanna: Renumeration-Dako, Noemarkers (Royalties).
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