Long-term survival analysis of addition of carboplatin to neoadjuvant chemotherapy in HER2-negative breast cancer

Breast Cancer Res Treat. 2020 Apr;180(3):687-694. doi: 10.1007/s10549-020-05580-y. Epub 2020 Mar 5.

Abstract

Purpose: Addition of carboplatin (CBDCA) to neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC) has improved pathological complete response (pCR) rates in previous studies. We present long-term survival outcomes (disease-free survival [DFS], pre-planned secondary endpoint; overall survival [OS], post hoc exploratory endpoint) of our randomized study of the addition of CBDCA to NAC for HER2-negative breast cancer.

Methods: Patients with stage II/III, HER2-negative breast cancer (N = 179) were randomly assigned to receive CP-CEF (four 3-week cycles of CBDCA [area under the curve, 5 mg/mL/min, day 1] and weekly paclitaxel [wPTX, 80 mg/m2, day 1, 8, 15] followed by four 3-week cycles of cyclophosphamide, epirubicin, and 5-fluorouracil [CEF, 500/100/500 mg/m2]) or P-CEF (four cycles of wPTX followed by four cycles of CEF) as NAC. DFS and OS were analyzed at each population of pCR status and assigned treatment arm.

Results: Of 179 patients, 154 were available for long-term follow-up. At a median follow-up of 6.6 years (range, 0.7-8.0 years), patients who achieved pCR [n = 42, 23.5% (CP-CEF: n = 28, P-CEF: n = 16)] had longer DFS and OS than non-pCR patients [DFS; HR 0.15 (0.04-0.61), P = 0.008, OS; log-rank P = 0.003]. Addition of carboplatin to NAC significantly improved DFS and OS in the subset of patients with TNBC [DFS: HR, 0.22 (0.06-0.82), P = 0.015; OS: HR, 0.12 (0.01-0.96), P = 0.046], but not in the subset of patients with hormone receptor-positive disease or among all patients.

Conclusions: Addition of carboplatin to neoadjuvant chemotherapy significantly improved DFS and OS in patients with TNBC but not in those with hormone receptor-positive, HER2-negative breast cancer.

Keywords: Carboplatin; Neoadjuvant chemotherapy; Pathological complete response; Triple-negative breast cancer.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / mortality*
  • Breast Neoplasms / pathology
  • Carboplatin / administration & dosage
  • Chemotherapy, Adjuvant / mortality*
  • Cyclophosphamide / administration & dosage
  • Epirubicin / administration & dosage
  • Female
  • Fluorouracil / administration & dosage
  • Follow-Up Studies
  • Humans
  • Middle Aged
  • Neoadjuvant Therapy / mortality*
  • Paclitaxel / administration & dosage
  • Prognosis
  • Receptor, ErbB-2 / metabolism*
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Survival Rate

Substances

  • Receptors, Estrogen
  • Receptors, Progesterone
  • Epirubicin
  • Cyclophosphamide
  • Carboplatin
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Paclitaxel
  • Fluorouracil