The Impact of Initial Tumor Response on Survival Outcomes of Patients With HER2-Positive Advanced Breast Cancer Treated With Docetaxel, Trastuzumab, and Pertuzumab: An Exploratory Analysis of the CLEOPATRA Trial

Clin Breast Cancer. 2024 Jul;24(5):421-430.e3. doi: 10.1016/j.clbc.2024.02.012. Epub 2024 Feb 21.

Abstract

Introduction: The CLEOPATRA trial (NCT00567190) established a dual anti-HER2 blockade in combination with docetaxel as the first-line standard of care for patients with metastatic HER2-positive breast cancer. While this treatment is overall associated with significant improvement in progression-free survival (PFS) and overall survival (OS), not all patients respond equally. We hypothesized that a radiological complete response (CR) at week 9 (i.e., first disease re-evaluation) is associated with prolonged OS and PFS compared to radiological partial response (PR) or stable disease (SD).

Methods: We performed an exploratory analysis of the CLEOPATRA study to address this question.

Results: Out of 362 patients treated with docetaxel, trastuzumab, and pertuzumab eligible for our analysis, 46 (12.7%) had radiological CR at week 9, 243 (67.1%) PR, and 73 (20.2%) SD per central RECIST v1.0. Radiological CR at first tumor re-evaluation was associated with a 60% risk reduction for death compared to SD (adjusted HR = 0.40 95% confidence interval (CI) 0.23-0.70), whereas no significant impact on survival was observed for PR (adjusted HR = 0.85 95% CI 0.60-1.20). The same was observed for PFS with adjusted HR = 0.30 (95% CI 0.18-0.48) for the CR subgroup and adjusted HR = 0.81 (95% CI 0.60-1.09) for the PR subgroup. In multivariate analysis, no variables were associated with radiological CR.

Conclusions: Our findings suggest that radiological CR at first disease re-evaluation is associated with more prolonged survival; this might result from stronger dependence on HER2 pathway addiction, supporting the need for further translational research.

Keywords: Complete response; HER2-positive breast cancer; Imaging.

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase III

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / mortality
  • Breast Neoplasms* / pathology
  • Docetaxel* / administration & dosage
  • Docetaxel* / therapeutic use
  • Female
  • Humans
  • Middle Aged
  • Progression-Free Survival
  • Receptor, ErbB-2* / metabolism
  • Trastuzumab* / therapeutic use

Substances

  • Docetaxel
  • pertuzumab
  • Trastuzumab
  • Receptor, ErbB-2
  • Antibodies, Monoclonal, Humanized
  • ERBB2 protein, human