Impact of Stopping Trastuzumab in Early Breast Cancer: A Population-Based Study in Ontario, Canada

• Published in: JNCI : Journal of the National Cancer Institute Vol. 112; no. 12; pp. 1222 - 1230
• Main Authors: Rushton, Moira, Lima, Isac, Tuna, Meltem, Johnson, Chris, Ivars, Josee, Pritchard, Kathy, Hawken, Steven, Dent, Susan
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 14.12.2020; Oxford Publishing Limited (England)
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - epidemiology; Breast Neoplasms - pathology; Cancer; Cardiotoxicity; Cardiovascular diseases; Cause of Death; Cohort Studies; Confidence intervals; Disease-Free Survival; Editor's Choice; ErbB-2 protein; Female; Health risks; Heart diseases; Heart Diseases - chemically induced; Heart Diseases - epidemiology; Heart Diseases - mortality; Humans; Immunotherapy; Medical imaging; Middle Aged; Monoclonal antibodies; Mortality; Neoplasm Recurrence, Local - epidemiology; Neoplasm Recurrence, Local - etiology; Neoplasm Staging; Ontario - epidemiology; Population studies; Population-based studies; Retrospective Studies; Sensitivity analysis; Statistical analysis; Stroke Volume - drug effects; Survival; Survival Analysis; Targeted cancer therapy; Trastuzumab; Trastuzumab - administration & dosage; Trastuzumab - adverse effects; Treatment Outcome; Ventricle; Ventricular Function, Left - drug effects; Withholding Treatment - statistics & numerical data; Young Adult; Ontario; Ontario Canada; Canada
• ISSN: 0027-8874; 1460-2105
• DOI: 10.1093/jnci/djaa054

Abstract Background Adjuvant trastuzumab for early-stage (I-III) HER2-positive breast cancer (BC) has led to statistically significant improvement in cancer outcomes but carries a risk of cardiotoxicity. Trastuzumab is discontinued early in many patients for asymptomatic changes in left ventricular ejection fraction. We evaluated the impact of early discontinuation of trastuzumab on cancer outcomes. Methods We conducted a retrospective population-based cohort study of early BC patients treated with adjuvant trastuzumab in Ontario, Canada, 2007-2016. Four groups were analyzed: group A was full treatment, 17-18 cycles trastuzumab; group B was cardiac event (CE) within treatment period; group C was ≤16 cycles, no CEs, stopped within 30 days from last cardiac imaging; and group D was ≤16 cycles, no CEs, stopped more than 30 days from cardiac imaging. Primary outcome was disease-free survival (DFS); secondary outcomes were: overall survival, cancer-specific mortality, and cardiovascular mortality. Sensitivity analyses were performed 14 months after cycle 1 trastuzumab to control for early relapse. Results A total of 5547 patients met the inclusion criteria: group A = 3921, group B = 309, group C = 362, and group D = 955. The 5-year DFS was 94.1% in group A, 80.1% in group B, 81.4% in group C, and 82.4% in group D. Using a Cox model, the hazard ratio for 5-year DFS was 3.15 (95% confidence interval [CI] = 2.13 to 4.65) for group B, 1.94 (95% CI = 1.30 to 2.89) for group C, and 1.92 (95% CI = 1.46 to 2.53) for group D. Overall, 26 patients (0.5%) died of cardiac causes. Conclusions BC patients in Ontario who did not complete adjuvant trastuzumab had a statistically significantly higher risk of BC relapse and death and low incidence of cardiac death. These findings support 1 year of adjuvant trastuzumab in early-stage BC.