Background

15-20% of breast cancers overexpress Human Epidermal Growth Factor Receptor 2 (HER2). Dual anti-HER2 monoclonal antibodies (Trastuzumab and Pertuzumab) with taxane is the standard of care as first-line treatment and antibody-drug conjugate Trastuzumab Emtansine (TDM-1) as second-line therapy for HER2-positive metastatic breast cancer (MBC). Beyond this, there is no standard of care and currently available treatments have limited benefit.

Method

We conducted a retrospective review on the management of HER2-positive MBC patients treated in two centres (Ipswich & Colchester) between 2013 and 2019. We included patients who received dual anti-HER2 therapy as first-line treatment and report on patient characteristics and outcome data including median progression free survival (PFS) on first and subsequent lines of therapy. Data was analysed using SPSS with log-rank test for significance analysis.

Results

73 patients received taxane with Pertuzumab and Trastuzumab for HER2-positive MBC as first-line treatment. The median PFS was 18 months, with a trend towards improved outcomes in ER-negative patients (16 months ER-positive versus 19 months ER-negative; p=0.172). 8 patients discontinued treatment due to adverse effects, 4 secondary to cardiotoxicity. 43 patients progressed on Pertuzumab and Trastuzumab with lung as the most common site of progression.

28/43 (65%) patients who progressed received TDM-1 as second-line treatment. The median PFS was 5 months with 22 patients progressing on TDM-1. 19/22 patients received 3rd-line treatment using a combination of chemotherapy ±Trastuzumab; Capecitabine (10 patients), Eribulin (4 patients). The median PFS on third-line treatment was 6 months. The median overall survival (OS) for the study population was 58.7 months.

Conclusion

We provide real world data on the outcomes for patients with HER2-positive MBC treated with dual anti-HER2 therapy. The median PFS of 18 months on first-line treatment and median OS of 58.7 months are similar to published trial results. The median PFS on second- and third-line treatment (post progression on dual anti-HER2 therapy) are poor, indicating need for better HER2-targeted therapy in these settings.

Impact statement

Our results highlight poor patient outcomes following progression on dual anti-HER2 treatment. It provides baseline real time data which can be used to compare efficacy of new therapeutic agents like Trastuzumab Deruxtecan approved in this setting.