Randomized Controlled Trial of Trastuzumab with or without Chemotherapy for HER2-Positive Early Breast Cancer in Older Patients

PURPOSE Adjuvant trastuzumab monotherapy has not been compared with trastuzumab 1 chemotherapy. We investigated the relative value of trastuzumab monotherapy for older patients with breast cancer. METHODS This study was an open-label, randomized controlled study with a treatment selection design in which a noninferiority criterion was predefined. Patients aged 70-80 years with surgically treated human epidermal growth factor receptor 2–positive invasive breast cancer received trastuzumab monotherapy or trastuzumab 1 chemotherapy. The primary end point was disease-free survival (DFS) with assessment of prespecified hazard ratio (HR), relapse-free survival (RFS), adverse events (AEs), health-related quality of life (HRQoL), and restricted mean survival time (RMST). RESULTS The study involved 275 patients (mean age, 73.5 years) who were followed up for a mean of 4.1 years (range, 0.3-8.0 years). The percentages of patients by cancer stage were as follows: I (pT . 0.5 cm), 43.6%; IIA, 41.7%; IIB, 13.5%; and IIIA, 1.1%. Three-year DFS was 89.5% with trastuzumab monotherapy versus 93.8% with trastuzumab 1 chemotherapy (HR, 1.36; 95% CI, 0.72 to 2.58; P 5 .51). At 3 years, RMST differed by 20.39 months between arms (95% CI, 21.71 to 0.93; P 5 .56). Three-year RFS was 92.4% with trastuzumab monotherapy versus 95.3% with trastuzumab 1 chemotherapy (HR, 1.33; 95% CI, 0.63 to 2.79; P 5 .53). Common AEs were anorexia (7.4% v 44.3%; P, .0001) and alopecia (2.2% v 71.7%; P, .0001), and grade 3/4 nonhematologic AEs occurred in 11.9% versus 29.8% (P 5 .0003) for trastuzumab monotherapy versus trastuzumab 1 chemotherapy, respectively. Clinically meaningful HRQoL deterioration rate showed significant differences at 2 months (31% for trastuzumab monotherapy v 48% for trastuzumab 1 chemotherapy; P 5 .016) and at 1 year (19% v 38%; P 5 .009). CONCLUSION The primary objective of noninferiority for trastuzumab monotherapy was not met. However, the observed loss of survival without chemotherapy was, 1 month at 3 years. Therefore, and in light of the lower toxicity and more favorable HRQoL profile, trastuzumab monotherapy can be considered an adjuvant therapy option for selected older patients.