Longer Duration of Adjuvant Trastuzumab May Further Improve DFS Rates in ERBB2-Positive Breast Cancer

Longer Duration of Adjuvant Trastuzumab May Further Improve DFS Rates in ERBB2-Positive Breast Cancer

One year of adjuvant trastuzumab (Herceptin), compared with 9 weeks, resulted in improved disease-free survival (DFS) in patients with ERBB2-positive breast cancer receiving chemotherapy, according to findings from the SOLD trial (NCT00593697) published in JAMA Network Open.

Of note, there was no significant difference in overall survival (OS) between the groups.

“The 9-week regimen may be an option for patients who may not tolerate 1-year trastuzumab or who cannot afford it,” study authors wrote.

Patients assigned to the 9-week group (n = 1085) had a shorter DFS than those assigned to the 1-year group (n = 1089; HR for recurrence or death: 1.36; 90% CI, 1.14-1.62; exploratory 2-sided log-rank superiority testing P = .004). The rates of OS were similar between the 9-week and 1-year groups at 5 years (95.0% vs 95.9%, respectively) and 10 years (89.1% vs 88.2%; HR for all time points = 1.20; 90% CI, 0.94-1.54).

Based on subgroup analyses, the size of the docetaxel starting dose (80 mg/m2 or 100 mg/m2) may have played a significant role in the differences in DFS by treatment group (P for interaction = .007).

Other factors associated with shorter DFS included 4 or more positive axillary nodes (HR = 2.28; 95% CI, 1.65-3.15; P = .001), disease stage of 2 or 3 vs 1 (HR = 1.53; 95% CI, 1.13-2.08; P = .006), and being in the 9-week group (HR = 1.36; 95% CI, 1.10-1.68; P = .005), although ER status, docetaxel starting dose, and age were not. This analysis did not result in a between-group difference regarding OS (HR = 1.22; 95% CI, 0.90-1.64; P = .20).

Four patients (0.2%) died of cardiac causes, including 3 deaths from coronary artery thrombosis and/or myocardial infarction and 1 death from heart failure. Of note, 3 of these patients had received 9 weeks of trastuzumab.

This post hoc secondary analysis of an open-label, multicenter, noninferiority-design randomized clinical trial included 2176 women aged 18 years or older with early ERBB2-positive breast cancer. Patients who were not included had a history of distant metastases or neoadjuvant therapy.

Patients were randomized 1:1 to receive either 9 weeks or 1 year of trastuzumab. All patients received 3 cycles of intravenous docetaxel (80 mg/m2 or 100 mg/m2) given in parallel with intravenous or subcutaneous trastuzumab, followed by 3 cycles of intravenous fluorouracil (600 mg/m2), epirubicin (75 mg/m2), and cyclophosphamide (600 mg/m2). All 6 dosing cycles were given at 3-week intervals. Patients received intravenous concomitant trastuzumab either weekly or at 3-week intervals, or subcutaneously every 3 weeks. Patients in the 1-year group received intravenous or subcutaneous trastuzumab every 3 weeks for 14 times after chemotherapy was stopped. Those in the 9-week group did not receive further trastuzumab after stopping chemotherapy.

The primary objective of this study was to assess DFS, defined as the time from randomization to the date when invasive cancer or death was detected. Distant DFS and OS were secondary objectives of this study.

This study represents the only randomized clinical trial that compared the 9-week and 1-year durations in a complete patient population other than the ShortHER trial (NCT00629278).

“Potential advantages of the 9-week regimen include little need for cardiac monitoring, fewer visits required for treatment administration, and lower cost. Access to trastuzumab is still a major barrier to care, particularly in low-income and lower-middle-income countries,” study authors wrote.

The main limitation of the study was the short follow-up time, allowing for unreported disease recurrence and breast cancer-related deaths. Additionally, 59.6% of patients had node-negative cancer, suggesting lack of generalizability.

Reference

Joensuu H, Fraser J, Wildiers H, et al. Long-Term Outcomes of Adjuvant Trastuzumab for 9 Weeks or 1 Year for ERBB2-Positive Breast Cancer: A Secondary Analysis of the SOLD Randomized Clinical Trial. JAMA Netw Open. 2024;7(8):e2429772. Published 2024 Aug 1. doi:10.1001/jamanetworkopen.2024.29772