Real world evidence for continuing HER2-directed therapy for metastatic breast cancer.
Authors: Jackson Emily Beatrice , LeVasseur Nathalie , Corke Lauren , Ohm Hyejee , Morris Aidan , Simmons Christine E. 
Published: June 2023

e18623 Background: Continuing HER2-directed therapy in metastatic breast cancer (MBC) beyond first line has been demonstrated to improve progression free survival (PFS) and overall survival (OS) in many randomized studies. Due to cost, many publicly funded health care systems restrict public funding to 2 lines of HER2 directed therapy (HER2Rx) in MBC. The purpose of this study is to assess the proportion of patients with HER2 positive MBC who were eligible to receive systemic therapy beyond second-line and successfully accessed continued HER2Rx despite lack of public funding. We also analyzed how the ability to access continued HER2Rx impacts survival. Methods: The BC Cancer Breast Cancer Outcomes Unit collects clinical, pathological and outcome data on patients diagnosed within BC. In addition, all publically funded anti-neoplastic therapy is recorded in the BC Cancer pharmacy database. These 2 databases were cross-referenced to identify patients who received any HER2Rx for MBC between 2013 and 2018, in the era where trastuzumab plus pertuzumab and TDM-1 were standard, publically available options. The number of lines of therapy received, treatment choice, and fitness to continue therapy beyond 2 lines were analyzed by manual chart review. Survival data was analyzed. Results: 571 patients met inclusion criteria. Median follow up was 47.6 months. Overall, 267 (47%) patients were eligible to continue therapy beyond second-line. Of these, 210 (37% of the whole cohort) accessed continued HER2-directed therapy, while 57 (10%) were eligible but unable to access continued HER2Rx. Of the remaining 304 patients in the total cohort, 110 patients (19%) had stable disease on continued first- or second-line therapy and 194 patients (34%) had deteriorating status precluding further treatment beyond second-line. The median lines of therapy in the entire study population was 3 (range 1-12). Median number of cycles of HER2-directed therapy received beyond second-line for those eligible to continue was 18 cycles. Median OS for those who continued HER2Rx was 59.7 months compared to 31.4 months for those who were eligible but unable to access continued HER2Rx; HR 0.42 (95% CI 0.31-0.58, p < 0.001). The vast majority of patients who continued to access HER2Rx did so through clinical trial or patient assistance programs, very rarely through private health insurance or out-of-pocket expenditures. Conclusions: Nearly half of patients with HER2 positive MBC were eligible to receive more than 2 lines of HER2 directed therapy. The majority of eligible patients do ultimately secure access despite prohibitive public funding policies. Receiving further HER2Rx was associated with a significant and clinically meaningful OS benefit of 28 months over those who go on to receive non-HER2 directed therapy. This survival advantage provides real-world evidence in support of the urgent need for more permissive public funding of HER2 directed therapy for MBC.