Clinical outcome of patients with isolated central nervous system progression on first-line pertuzumab and trastuzumab treatment for HER2-positive metastatic breast cancer in a real-life cohort

Breast Cancer. 2023 Mar;30(2):329-341. doi: 10.1007/s12282-022-01427-0. Epub 2023 Jan 11.

Abstract

Background: More than 10% of HER2-positive metastatic breast cancer (mBC) will develop Central Nervous System (CNS) metastases as first and isolated site of relapse on trastuzumab and pertuzumab first-line therapy. However, few clinical data are available to guide the best strategy in this setting.

Methods: Patients experiencing isolated CNS progression on trastuzumab and pertuzumab first-line therapy were retrospectively identified from the French Epidemiological Strategy and Medical Economics (ESME) real-life database between 2008 and 2016.

Results: Among 995 patients treated with first-line trastuzumab and pertuzumab for HER2-positive mBC, 132 patients (13%) experienced isolated CNS progression with a median time of 12 months after mBC diagnosis. Twelves patients did not receive any treatment and were excluded from the analysis. Among the 120 patients considered, 76 (63%) received CNS-directed local therapy, 73 (60%) continued trastuzumab and pertuzumab, whereas 47 (39%) started another systemic treatment. After a median follow-up of 21 months, there was no difference in progression-free survival for patient who continued trastuzumab-pertuzumab or switched to another systemic treatment. In multivariate analysis, trastuzumab-pertuzumab continuation was associated with longer OS (HR 0,28 IC 95%: 0,14-0,54 p < 0,001). mOS was not reached (95% 37.6-NE) and was 23.2 months (95% CI 15.5-53.6) in patients who continued trastuzumab and pertuzumab therapy and in patients who switched for another systemic therapy, respectively.

Conclusion: In this real-life cohort, trastuzumab-pertuzumab continuation after local treatment for isolated CNS progression did not negatively impact PFS and OS. Prospective trials and assessment of new strategies are warranted in this specific situation.

Keywords: Brain metastases; Breast neoplasms; Pertuzumab; Trastuzumab; Tyrosine kinase-type cell surface receptor HER2.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Breast Neoplasms* / pathology
  • Central Nervous System / pathology
  • Female
  • Humans
  • Neoplasm Recurrence, Local / drug therapy
  • Prospective Studies
  • Receptor, ErbB-2
  • Retrospective Studies
  • Trastuzumab / therapeutic use
  • Treatment Outcome

Substances

  • Trastuzumab
  • pertuzumab
  • Receptor, ErbB-2