Real world outcomes in elderly women with HER2 positive advanced breast cancer

Abstract

Background The development of anti-human epidermal growth factor receptor 2 (HER2) therapies has significantlyimproved disease outcomes in patients with HER2-positive advanced breast cancer (ABC). However, elderlypatients are persistently under-represented in clinical trials, with only 2.4% of patients aged >=75 years in the pivotalCLEOPATRA study. Despite a lack of research addressing treatment outcomes in elderly patients, advanced age atdiagnosis is associated with a greater likelihood of receiving no initial systemic therapy for de novo metastatic breastcancer. Studies have also shown that older women diagnosed with metastatic breast cancer have a poorerprognosis and shorter life expectancy. We examined treatment patterns and outcomes in an elderly (defined as >=70)'real world' Australian population. Methods Data was extracted from the Treatment of Advanced Breast Cancer in the HER2-positive Australian Patient(TABITHA) multi-site clinical registry, and patients stratified according to age (<70 and >=70 years). Descriptivestatistics were used to report baseline characteristics and compared using T-tests and Chi square analyses.Treatment duration and overall survival were calculated via the Kaplan-Meier method using GraphPad Prism 8.0software. Results We identified 319 patients, including 67 patients (21%) aged >=70 years. Older patients were more likely tohave an Eastern Cooperative Oncology Group performance status of >=2 (16% vs 3%; p<0.001) and a Charlson Comorbidity Index of >=2 (13% vs 7%; p<0.001). There were no significant differences in hormone receptor status, denovo metastatic presentation, or presence of visceral disease between groups. A similar proportion of patients ineach group received first line HER2-directed therapy (85% vs 93%; p=0.054), and the duration of therapy was notsignificantly different between groups (16 vs 22 months; p=0.70). Despite no difference between groups in theproportion of patients who received first-line chemotherapy, older patients demonstrated shorter chemotherapydurations (2.7 months vs 3.5 months; p<0.02). Median overall survival was significantly longer in younger patients(82 months vs 42 months; hazard ratio, 0.50; 95%CI, 0.29-0.87; p<0.001). In the first-line setting, overall adverseevents rates were higher in the older group (34% vs 20%; p=0.04), including cardiotoxicity (7% vs 0.9%; p=0.02),and on-treatment deaths (5% vs 0%; p=0.01). Conclusion Elderly patients with HER2-positive ABC demonstrated shorter chemotherapy durations, poorer overallsurvival, and increased rates of adverse events despite having similar disease characteristics and treatmentpatterns. Prospective studies are required to improve outcomes in the elderly HER2 positive population.