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

Abstract

PURPOSE Adjuvant trastuzumab monotherapy has not been compared with trastuzumab + 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 + 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 + chemotherapy (HR, 1.36; 95% CI, 0.72 to 2.58; P = .51). At 3 years, RMST differed by −0.39 months between arms (95% CI, −1.71 to 0.93; P = .56). Three-year RFS was 92.4% with trastuzumab monotherapy versus 95.3% with trastuzumab + chemotherapy (HR, 1.33; 95% CI, 0.63 to 2.79; P = .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 = .0003) for trastuzumab monotherapy versus trastuzumab + chemotherapy, respectively. Clinically meaningful HRQoL deterioration rate showed significant differences at 2 months (31% for trastuzumab monotherapy v 48% for trastuzumab + chemotherapy; P = .016) and at 1 year (19% v 38%; P = .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.

Tolerability and toxicity of trastuzumab or trastuzumab + lapatinib in older patients: a sub-analysis of the ALTTO trial (BIG 2-06; NCCTG (Alliance) N063D)

“…Both concomitant use of chemotherapy, and the standard regimen used today increased the need for temporary treatment interruptions. Interestingly, the RESPECT trial, which evaluated the efficacy of adjuvant trastuzumab alone vs trastuzumab + chemotherapy in patients 70 year of age or older, suggests trastuzumab monotherapy to be better tolerated (in terms of AEs and quality of life), and that outcomes with monotherapy are inferior only a small amount [24]. Polypharmacy was also identified in our dataset as a predictor of worse treatment completion outcomes.…”

Adjuvant Trastuzumab Without Chemotherapy For Treating Early HER2-Positive Breast Cancer In Older Patients: A Cohort Study Accompanying With The RESPECT Trial

“…Thus, it was considered possible to include 200 patients in the RCT over 4 years. The DFS was set as the primary endpoint, as was done for the RCT of the RESPECT study [1].…”

“…The RESPECT study is the rst randomized adjuvant trial comparing trastuzumab monotherapy with trastuzumab-plus-chemotherapy for patients with HER2-positive breast cancer [1]. The RESPECT study was accompanied by a cohort study for patients who refused to participate in the RCT.…”

“…Patients who did not agree to participate in the RCT (despite meeting the eligibility criteria and being given an explanation of the RCT by the investigator) were included in the cohort study with written informed consent. Patients who consented to participate in the RCT were randomly assigned at a 1:1 ratio to the trastuzumab monotherapy group or trastuzumab-plus-chemotherapy group [1]. In this cohort study, treatment was chosen based on the discretion of the treating physician and the patients' wishes without intervention, and patients were prospectively surveyed based on routine medical records.…”

Cost-efficiency and expanded access modeling of conversion to biosimilar trastuzumab-dkst with or without pertuzumab in metastatic breast cancer

“…Additionally, trastuzumab A c c e p t e d M a n u s c r i p t monotherapy is approved for treating patients with MBC who have received one or more chemotherapy regimens. It is also used in the adjuvant setting without chemotherapy in selected older patient populations [15,16]; as well as in the neoadjuvant or adjuvant settings for patients with early HER2+ breast cancer [17,18]. Recent real-world studies suggest significant disparities in access to anti-HER2 therapy in resource-limited communities due, in part, to the high cost of trastuzumab [19,20].…”