Survival before and after the introduction of pertuzumab and T-DM1 in HER2-positive advanced breast cancer, a study of the SONABRE Registry

Khava I E Ibragimova, Sandra M E Geurts, Sander Croes, 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 van de Winkel, Dominique J P Tilli, Ingeborg J H Vriens, Maaike de Boer, Vivianne C G Tjan-Heijnen, Khava I E Ibragimova, Sandra M E Geurts, Sander Croes, 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 van de Winkel, Dominique J P Tilli, Ingeborg J H Vriens, Maaike de Boer, Vivianne C G Tjan-Heijnen

Abstract

Purpose: Immediate and proper implementation of a new and more potent therapy is important to ensure that the patient achieves the best possible outcome. This study aimed to examine whether the real-world overall survival (OS) has improved in patients with human epidermal growth factor receptor 2-positive (HER2 +) advanced breast cancer (ABC) since the market release of pertuzumab and T-DM1. Furthermore, we aimed to assess the implementation and survival rates per hormone receptor (HR) subtype.

Patients and methods: We included 493 systemically treated patients consecutively diagnosed with HER2 + ABC in 2008-2017 from the SOutheast Netherlands Advanced BREast cancer (SONABRE) Registry. Median OS was obtained using the Kaplan-Meier method and differences between periods (2008-2012 versus 2013-2017) were tested using multivariable Cox proportional hazards regression modeling. The 3-year implementation rates were estimated for any HER2-targeted therapy, pertuzumab, and T-DM1 by using the competing risk method and calculated from the date of diagnosis of ABC to start of HER2-targeted therapy of interest.

Results: The median OS in 2008-2012 versus 2013-2017 was 28.3 versus 39.7 months in all patients (adjusted hazard ratio (adjHR) 0.85, 95%CI 0.66-1.08), 29.9 versus 36.3 months in patients with HR + /HER2 + disease (adjHR 0.97, 95%CI 0.72-1.32), and 22.7 versus 40.9 months in patients with HR-/HER2 + disease (adjHR 0.59, 95%CI 0.38-0.92). Any HER2-targeted therapy was used in 79% of patients in 2008-2012 and in 84% in 2013-2017. The use of pertuzumab and T-DM1 in 2013-2017 was 48% and 29%, respectively. For patients diagnosed with HR + /HER2 + and HR-/HER2 + disease, implementation rates in 2013-2017 were , respectively, 77% and 99% for any HER2-targeted therapy, 38% and 69% for pertuzumab, and 24% and 40% for T-DM1.

Conclusion: The survival of patients with HER2 + ABC improved since the introduction of pertuzumab and T-DM1. There is room for improvement in implementation of these HER2-targeted therapies, especially in patients with HR + /HER2 + disease.

Keywords: Breast neoplasms; HER2-positive disease; Metastatic breast cancer; Pertuzumab; Survival; T-DM1.

Conflict of interest statement

Khava I.E. Ibragimova Netherlands Organization for Health Research and Development (ZonMw: 80–82500-98–8003); Novartis BV; Roche; Pfizer; Eli Lilly. Sandra M.E. Geurts Netherlands Organization for Health Research and Development (ZonMw: 80–82500-98–8003); Novartis BV; Roche; Pfizer; Eli Lilly. Dominique J.P. Tilli Netherlands Organization for Health Research and Development (ZonMw: 80–82500-98–8003); Novartis BV; Roche; Pfizer; Eli Lilly. Maaike de Boer Netherlands Organization for Health Research and Development (ZonMw: 80–82500-98–8003); Novartis BV; Roche; Pfizer; Eli Lilly. Vivianne C.G. Tjan-HeijnenNetherlands Organization for Health Research and Development (ZonMw: 80–82500-98–8003); Novartis BV; Roche; Pfizer; Eli Lilly. All remaining authors have declared no conflicts of interest.

Figures

Fig. 1
Fig. 1
Flow chart study population
Fig. 2
Fig. 2
Overall survival in patients systemically treated for a HER2 + , b HR + /HER2 + , c HR-/HER2 + ABC by incidence period of ABC diagnosis
Fig. 3
Fig. 3
Use of a–c any HER2-targeted therapy, d–f pertuzumab-based therapy, and g–i T-DM1 in systemically treated patients and categorized by incidence period and hormone receptor status of

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