As reported in the Journal of Clinical Oncology by PierFranco Conte, MD, PhD, and colleagues, the final analysis of the Italian phase III noninferiority ShortHER trial showed little difference in 10-year disease-free survival and overall survival with 9 weeks vs 1 year of adjuvant trastuzumab in patients with HER2-positive breast cancer. Outcomes favored longer treatment among patients with greater nodal involvement.
Study Details
In the multicenter trial, 1,254 patients were randomly assigned to receive adjuvant anthracycline/taxane combinations plus 9 weeks of weekly trastuzumab (short group, n = 627) or trastuzumab every 3 weeks for 18 doses (long group, n = 627). In the previously reported primary analysis of disease-free survival, the hazard ratio for the short group vs the long group was 1.13 (90% confidence interval [CI] = 0.89–1.42); noninferiority could not be claimed since the upper bound of the confidence interval crossed the noninferiority margin of 1.29.
PierFranco Conte, MD, PhD
Key Findings
Median follow-up for the final analysis was 9 years.
Disease-free survival at 10 years was 78% in the short group vs 77% in the long group (HR = 1.06, 95% CI = 0.83–1.36). For the short group vs the long group, according to nodal involvement, 10-year disease-free survival was 85% vs 81% for N0 status (HR = 0.75, 95% CI = 0.51–1.10), 79% vs 77% for N1 to 3 status (HR = 1.11, 95% CI = 0.70–1.76), and 53% vs 63% for N4+ status (HR = 1.84, 95% CI = 1.14–2.97).
Overall survival at 10 years was 88% in the short group vs 89% in the long group (HR = 1.15, 95% CI = 0.80–1.65). According to nodal involvement, 10-year overall survival was 95% vs 89% for N0 status (HR = 0.57, 95% CI = 0.30–1.10), 89% vs 92% for N1 to 3 status (HR = 1.37, 95% CI = 0.69–2.73), and 64% vs 84% for N4+ status (HR = 1.87, 95% CI =1.01–3.46).
The investigators concluded, “The updated analysis of the ShortHER trial shows that 1-year trastuzumab is the standard treatment for patients with HER2-positive early breast cancer as noninferiority cannot be claimed. However, numerically, the differences for the patients at low or intermediate risk (N0/N1–3) is negligible, while patients with N4+0 have a clear benefit with 1-year trastuzumab.”
Dr. Conte, of San Camillo Hospital, IRCCS, Venezia, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the Agenzia Italiana del Farmaco. For full disclosures of the study authors, visit ascopubs.org.
