Treatment-related acute toxicity with adjuvant systemic treatment among patients with HER2-positive early invasive breast cancer: a national population-based cohort study.

Objective: Although adjuvant trastuzumab-based treatment (TBT) improves survival for patients with HER2-positive early invasive breast cancer (EIBC), risk of toxicity grows as patient age increases. We examined use of TBT and associated severe acute toxicity event (SATE) rates to understand the real-world impact. Methods and analysis: Women (50+ years), newly diagnosed with HER2-positive EIBC in England, 2014-2019, were identified from Cancer Registry data, linked to the Systemic Anti-Cancer Therapy dataset for TBT information. SATEs were measured using hospital administrative data. Statistical models were developed to identify potential predictors of SATE. Results: Among 5087 women who received trastuzumab, with median duration 11.7 months, 47.4% (95% CI 46.0% to 48.7%) completed treatment. Women aged 70+ years made up 20.2% of patients aged 50+ who received adjuvant TBT in routine care, compared with 5% of women aged 50+ across trials. 32.8% (95% CI 31.5% to 34.1%) had a record of any SATE. 6.8% (95% CI 6.1% to 7.5%) had a cardiovascular SATE. Congestive cardiac failure rate was 0.5% (95% CI 0.3% to 0.7%). High deprivation, anthracycline use, increasing frailty were associated with increased odds of any SATE. Older age, sequential chemotherapy, history of myocardial infarction/chronic pulmonary disorder/liver disease were associated with increased odds of cardiovascular SATE. Among two-thirds of women not eligible for trial cohorts SATE rates were lower than for trial-eligible patients, explained by baseline differences in patients. Conclusion: Evidence of treatment-related SATE among patients treated in routine care is needed to inform treatment decisions and counsel older patients. This study provides information on SATE rates for adjuvant TBT, and common types, overall and by age for such discussions.