Trastuzumab Resistance in Patients With HER2-Positive Advanced Breast Cancer: Results From the SONABRE Registry

Khava I E Ibragimova, Sandra M E Geurts, Dávid Laczkó, Marissa Meegdes, Frans Erdkamp, Joan B Heijns, Jolien Tol, Birgit E P J Vriens, Kirsten N A Aaldering, Marcus W Dercksen, Manon J A E Pepels, Natascha A J B Peters, Linda M H van de Winkel, Agnes J van de Wouw, Aude de Fallois, Maartje A C E van Kats, Vivianne C G Tjan-Heijnen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

BACKGROUND: This study aims to explore whether first-line pertuzumab use modifies the effect of prior use of (neo-) adjuvant trastuzumab on the PFS of first-line HER2-targeted therapy in patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer (ABC). METHODS: Patients diagnosed with HER2-positive ABC in 2008 to 2018 in 9 Dutch hospitals were derived from the SONABRE Registry (NCT03577197). Patients diagnosed with de novo metastatic breast cancer were excluded. Patients receiving first-line trastuzumab-based therapy for ABC were selected and divided into trastuzumab naïve (n = 113) and trastuzumab pretreated (n = 112). Progression-free survival (PFS) was compared using multivariable Cox proportional hazard models. The interaction effect of first-line pertuzumab was tested using the likelihood-ratio test. RESULTS: The median follow-up time was 47 months (95% confidence interval [CI]: 42-52). When comparing trastuzumab pretreated with trastuzumab naïve patients, the hazard ratio for first-line progression was 2.07 (CI:1.47-2.92). For trastuzumab pretreated patients who received first-line trastuzumab without pertuzumab, the hazard ratio for progression was 2.60 (95% CI:1.72-3.93), whereas for those who received first-line trastuzumab with pertuzumab the hazard ratio was 1.43 (95% CI: 0.81-2.52) (P interaction = .10). CONCLUSIONS: Prior use of trastuzumab as (neo-)adjuvant treatment had a negative impact on PFS of first-line HER2-targeted therapy outcomes. Adding pertuzumab to first-line trastuzumab-based therapy decreased the negative impact of prior (neo-)adjuvant trastuzumab use on first-line PFS. Further studies are needed to assess the effect of prior (neo-)adjuvant pertuzumab use on the outcomes of first-line pertuzumab-based therapy.
Original languageEnglish
Pages (from-to)103-111
Number of pages9
JournalClinical Breast Cancer
Volume24
Issue number2
Early online date2 Nov 2023
DOIs
Publication statusPublished - Feb 2024

Keywords

  • HER2 positive disease
  • Metastatic breast cancer
  • Pertuzumab
  • Progression

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