According to findings from a phase III randomized trial reported by Zhang et al in the Journal of Clinical Oncology, the novel HER2-directed antibody-drug conjugate trastuzumab botidotin significantly prolonged progression-free survival compared with ado-trastuzumab emtansine (T-DM1) in patients with HER2-positive unresectable or metastatic breast cancer previously treated with trastuzumab and a taxane.
Study Details
The open-label, multicenter trial enrolled adults aged 18 to 75 years with HER2-positive unresectable or metastatic breast cancer that had progressed after at least one trastuzumab-based regimen and prior taxane therapy. Between July 2023 and April 2024, 365 patients treated at 57 centers in China were randomly assigned 1:1 to receive trastuzumab botidotin at 4.8 mg/kg every 3 weeks (n = 182) or T-DM1 at 3.6 mg/kg every 3 weeks (n = 183). The primary endpoint was progression-free survival assessed by blinded independent central review.
The median age was 55 years (interquartile range = 48–60 years), 73.4% of patients had visceral metastases, 53.4% had received at least two prior lines of anti-HER2 therapy, 46.0% had previously received pertuzumab, and 59.5% had received an anti-HER2 tyrosine kinase inhibitor.
Key Results
At a median follow-up of 14.9 months, median progression-free survival assessed by blinded independent central review was 11.1 months with trastuzumab botidotin vs 4.4 months with T-DM1 (hazard ratio [HR] = 0.39, 95% confidence interval [CI] = 0.30–0.51, nominal P < .0001). Estimated 6-month progression-free survival rates were 69.7% and 39.7%, respectively. The progression-free survival benefit was consistent across prespecified subgroups.
The objective response rate was 76.9% (95% CI = 70.1%–82.8%) with trastuzumab botidotin vs 53.0% (95% CI = 45.5%–60.4%) with T-DM1. Median duration of response was 12.2 vs 5.7 months, respectively. Overall survival data remained immature, with median overall survival not reached in either group (HR = 0.62, 95% CI = 0.38–1.03).
Grade 3 or higher treatment-emergent adverse events occurred in 69.8% of patients receiving trastuzumab botidotin and 63.7% receiving T-DM1. Ocular treatment-related adverse events were prominent with trastuzumab botidotin, including corneal disorders in 92.9% and dry eye in 61.5% of patients. However, none of these common ocular events led to treatment discontinuation, and nearly all grade 3 or higher ocular events improved to grade 2 or lower with protocol-defined management. Treatment-related interstitial lung disease or pneumonitis occurred in 1.1% and 2.7% of patients, respectively.
“Among patients with HER2-positive advanced [breast cancer] previously treated with trastuzumab and a taxane, trastuzumab botidotin resulted in significantly longer [progression-free survival] than [T-DM1], with a distinct safety profile,” the authors concluded.
Xichun Hu, MD, of the Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China, is the corresponding author for the Journal of Clinical Oncology article.
DISCLOSURE: The study was supported by the Noncommunicable Chronic Diseases-National Science and Technology Major Project, National Natural Science Foundation of China, and Sichuan Kelun-Biotech Biopharmaceutical Co, Ltd. For full disclosures of the study authors, visit ascopubs.org.
