Neoadjuvant chemotherapy using nanoparticle albumin-bound paclitaxel plus trastuzumab and pertuzumab followed by epirubicin and cyclophosphamide for operable HER2-positive primary breast cancer: a multicenter phase II clinical trial (PerSeUS-BC04)

Breast Cancer. 2023 Mar;30(2):293-301. doi: 10.1007/s12282-022-01425-2. Epub 2023 Jan 7.

Abstract

Background: Nanoparticle albumin-bound paclitaxel (nab-PTX) is a promising antibody partner for anti-human epidermal growth factor receptor 2 (HER2). We performed neoadjuvant chemotherapy (NAC) for HER2-positive breast cancer (BC) using nab-PTX plus trastuzumab (T-mab) and pertuzumab (P-mab), followed by epirubicin and cyclophosphamide (EC).

Methods: In this multicenter phase II clinical trial (January 2019-July 2020), patients with stage I (T1c)-IIIB HER2-positive primary BC were treated with four cycles of nab-PTX plus T-mab and P-mab, followed by four cycles of EC. The primary endpoint was the pathological complete response (pCR) rate. Secondary endpoints were clinical response rate (RR), adverse events (AE), and tumor-infiltrating lymphocytes (TILs) in biopsy samples.

Results: In total, 43 patients were enrolled (mean age, 54 years). Twenty-two patients had HER2, and 21 patients had luminal/HER2-subtypes. The overall pCR rate was 53.5% (23/43, 95% CI: 42.6-64.1%, p = 0.184), whilst the pCR for HER2 was 68.2% (15/22, 95% CI: 45.1-86.1) and 38.1% for luminal/HER2 (8/21, 95% CI: 18.1-61.6%). The RR was 100% [clinical (c) CR:25, partial response (PR): 18]. AEs (≥ G3) included neutropenia (23.3%), leukopenia (7.0%), liver dysfunction (7.0%), and peripheral neuropathy (4.7%) when nab-PTX was administered. EC administration resulted in leukopenia (34.2%), neutropenia (31.6%), and febrile neutropenia (15.8%). The TILs in preoperative biopsy samples were significantly higher in pCR compared to non-pCR samples.

Conclusion: Nab-PTX plus T-mab and P-mab induced a high pCR rate in HER2-positive BC, particularly in the HER2-subtype. Given that AEs are acceptable, this regimen is safe and acceptable as NAC for HER2-positive BC.

Keywords: Albumin-bound paclitaxel (Nab-PTX); HER2-positive breast cancer; Neoadjuvant chemotherapy; Pertuzumab; Trastuzumab.

Publication types

  • Multicenter Study
  • Clinical Trial, Phase II

MeSH terms

  • Albumin-Bound Paclitaxel
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Breast Neoplasms* / pathology
  • Cyclophosphamide / adverse effects
  • Epirubicin / adverse effects
  • Female
  • Humans
  • Middle Aged
  • Nanoparticles*
  • Neoadjuvant Therapy
  • Neutropenia* / chemically induced
  • Paclitaxel / adverse effects
  • Receptor, ErbB-2 / metabolism
  • Trastuzumab / adverse effects

Substances

  • Trastuzumab
  • Albumin-Bound Paclitaxel
  • Epirubicin
  • pertuzumab
  • Paclitaxel
  • Receptor, ErbB-2
  • Cyclophosphamide