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.

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.

• 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
• Journal: Breast cancer research and treatment (Breast Cancer Res Treat) Vol. 169 Issue 2 Pg. 333-340 (Jun 2018) ISSN: 1573-7217 [Electronic] Netherlands
• PMID: 29396664 (Publication Type: Clinical Trial, Phase II, Journal Article)

Chemical References

• Antibodies, Monoclonal, Humanized
• Bridged-Ring Compounds
• Taxoids
• taxane
• Epirubicin
• Cyclophosphamide
• ERBB2 protein, human
• Receptor, ErbB-2
• pertuzumab
• Trastuzumab
• Paclitaxel
• Fluorouracil

Topics

• Adult
• Antibodies, Monoclonal, Humanized (administration & dosage, adverse effects)
• Breast Neoplasms (drug therapy, epidemiology, genetics, pathology)
• Bridged-Ring Compounds (administration & dosage, adverse effects)
• Cyclophosphamide (administration & dosage, adverse effects)
• Drug-Related Side Effects and Adverse Reactions (classification, pathology)
• Epirubicin (administration & dosage, adverse effects)
• Female
• Fluorouracil (administration & dosage, adverse effects)
• Humans
• Middle Aged
• Neoadjuvant Therapy (adverse effects)
• Paclitaxel (administration & dosage, adverse effects)
• Receptor, ErbB-2 (genetics)
• Taxoids (administration & dosage, adverse effects)
• Trastuzumab (administration & dosage, adverse effects)