Outcomes for the first four lines of therapy in patients with HER2-positive advanced breast cancer: results from the SONABRE registry

Abstract

Purpose: We assessed the systemic treatment choices and outcomes in patients diagnosed with human epidermal growth factor receptor-2-positive (HER2 +) advanced breast cancer (ABC), for the first four lines of systemic therapy and by hormone receptor (HR) status.

Methods: We identified 330 patients diagnosed with HER2 + ABC in 2013-2018 in the Southeast of The Netherlands, of whom 64% with HR + /HER2 + and 36% with HR-/HER2 + disease. Overall survival (OS) from start of therapy was calculated using the Kaplan-Meier method.

Results: In real world, 95% of patients with HR + /HER2 + and 74% of patients with HR-/HER2 + disease received systemic therapy. In HR + /HER2 + disease, use of endocrine, chemo- and HER2-targeted therapy was , respectively, 64%, 46% and 60% in first line, and 39%, 64% and 75% in fourth line. In HR-/HER2 + disease, 91-96% of patients received chemotherapy and 77-91% HER2-targeted therapy, irrespective of line of therapy. In patients with HR + /HER2 + disease, median OS was 34.9 months (95%CI:25.8-44.0) for the first line and 12.8 months (95%CI:10.7-14.9) for the fourth line. In HR-/HER2 + disease, median OS was 39.9 months (95%CI:23.9-55.8) for the first line and 15.2 months (95%CI:10.9-19.5) for the fourth line. For patients treated with first-line pertuzumab, trastuzumab plus chemotherapy, median OS was not reached at 56.0 months in HR + /HER2 + disease and 48.4 months (95%CI:32.6-64.3) in HR-/HER2 + disease.

Conclusion: Survival times for later lines of therapy are surprisingly long and justify the use of multiple lines of systemic therapy in well-selected patients with HER2 + ABC. Our real-world evidence adds valuable observations to the accumulating evidence that within HER2 + ABC, the HR status defines two distinct disease subtypes.

Keywords: Breast neoplasms; ERBB2 protein; Neoplasm metastasis; Pertuzumab; Registries; Treatment Outcome.

Fig. 1

Flowchart patient selection

Fig. 2

Treatment pattern of patients diagnosed with HER2 + ABC, categorized by HR status. ABC advanced breast cancer, CT chemotherapy, ET endocrine therapy, HER2 Human Epidermal growth factor Receptor 2, HER2-TT HER2-targeted therapy, HR hormone receptor. ^§Proportion of patients with HR + /HER2 + disease treated with endocrine (± HER2-targeted) maintenance therapy per line of therapy: 1st line N = 27 (13%); 2nd line N = 4 (3%); 3rd line N = 0; 4th line N = 2 (4%). *Includes patients (N = 3) treated with endocrine-based therapy with HR + primary breast tumour

Fig. 3

Progression-free survival (PFS) and overall survival (OS) per systemic line of therapy, categorized by HR status

Fig. 4

Progression-free survival (PFS) and overall survival (OS) of the most common first-line treatment regimens*, categorized by HR status. CT chemotherapy, ET endocrine therapy, HER2 Human Epidermal growth factor Receptor 2, HER2-TT HER2-targeted therapy, HR hormone receptor, P pertuzumab, T trastuzumab. *Note, not to be directly compared because of risk of confounding by indication. See also Supplement Table S2 for the outcomes of all types of treatment regimes