Neoadjuvant anthracycline-based (5-FEC) or anthracycline-free (docetaxel/carboplatin) chemotherapy plus trastuzumab and pertuzmab in HER2 + BC patients according to their TOP2A: a multicentre, open-label, non-randomized phase II trial

Breast Cancer Res Treat. 2024 Jun;205(2):267-279. doi: 10.1007/s10549-024-07285-y. Epub 2024 Mar 7.

Abstract

Purpose: Previous studies have reported the benefit of dual HER2-targeting combined to neoadjuvant chemotherapy in HER2-amplified breast cancer (HER2 + BC). Moreover, besides the cardiac toxicity following their association to Trastuzumab, anthracyclines chemotherapy may not profit all patients. The NeoTOP study was designed to evaluate the complementary action of Trastuzumab and Pertuzumab, and the relevance of an anthracycline-based regimen according to TOP2A amplification status.

Methods: Open-label, multicentre, phase II study. Eligible patients were aged ≥ 18 with untreated, operable, histologically confirmed HER2 + BC. After centralized review of TOP2A status, TOP2A-amplified (TOP2A+) patients received FEC100 for 3 cycles then 3 cycles of Trastuzumab (8 mg/kg then 6 mg/kg), Pertuzumab (840 mg/kg then 420 mg/kg), and Docetaxel (75mg/m2 then 100mg/m2). TOP2A-not amplified (TOP2A-) patients received 6 cycles of Docetaxel (75mg/m2) and Carboplatin (target AUC 6 mg/ml/min) plus Trastuzumab and Pertuzumab. Primary endpoint was pathological Complete Response (pCR) using Chevallier's classification. Secondary endpoints included pCR (Sataloff), Progression-Free Survival (PFS), Overall Survival (OS), and toxicity.

Results: Out of 74 patients, 41 and 33 were allocated to the TOP2A + and TOP2A- groups respectively. pCR rates (Chevallier) were 74.4% (95%CI: 58.9-85.4) vs. 71.9% (95%CI: 54.6-84.4) in the TOP2A + vs. TOP2A- groups. pCR rates (Sataloff), 5-year PFS and OS were 70.6% (95%CI: 53.8-83.2) vs. 61.5% (95%CI: 42.5-77.6), 82.4% (95%CI: 62.2-93.6) vs. 100% (95%CI: 74.1-100), and 90% (95%CI: 69.8-98.3) vs. 100% (95%CI: 74.1-100). Toxicity profile was consistent with previous reports.

Conclusion: Our results showed high pCR rates with Trastuzumab and Pertuzumab associated to chemotherapy. They were similar in TOP2A + and TOP2A- groups and the current role of neoadjuvant anthracycline-based chemotherapy remains questioned.

Trial registration number: NCT02339532 (registered on 14/12/14).

Keywords: HER2-positive breast Cancer (HER2 + BC); Pathological complete response (pCR); Pertuzumab; TOP2A; Trastuzumab.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Anthracyclines / administration & dosage
  • Anthracyclines / therapeutic use
  • Antibodies, Monoclonal, Humanized* / administration & dosage
  • Antibodies, Monoclonal, Humanized* / adverse effects
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / mortality
  • Breast Neoplasms* / pathology
  • Carboplatin* / administration & dosage
  • Carboplatin* / adverse effects
  • Cyclophosphamide / administration & dosage
  • DNA Topoisomerases, Type II* / genetics
  • DNA Topoisomerases, Type II* / metabolism
  • Docetaxel* / administration & dosage
  • Docetaxel* / adverse effects
  • Epirubicin / administration & dosage
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Fluorouracil / therapeutic use
  • Humans
  • Middle Aged
  • Neoadjuvant Therapy*
  • Poly-ADP-Ribose Binding Proteins / genetics
  • Receptor, ErbB-2* / metabolism
  • Trastuzumab* / administration & dosage
  • Trastuzumab* / adverse effects
  • Trastuzumab* / therapeutic use

Substances

  • pertuzumab
  • TOP2A protein, human
  • ERBB2 protein, human

Supplementary concepts

  • FEC protocol

Associated data

  • ClinicalTrials.gov/NCT02339532