Datopotamab deruxtecan versus chemotherapy in previously treated inoperable/metastatic hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer: results from the TROPION-Breast01 China cohort

Abstract

Background In the global phase III TROPION-Breast01 study, datopotamab deruxtecan (Dato-DXd) demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) by blinded independent central review (BICR) versus investigator’s choice of chemotherapy (ICC) in patients with previously treated, inoperable/metastatic hormone receptor(HR)-positive human epidermal growth factor receptor 2-negative (HR+/HER2—) breast cancer. At the final analysis, overall survival (OS) was not statistically significant. We report final results from the prespecified analysis of patients enrolled in mainland China. Patients and methods Patients with inoperable/metastatic HR+/HER2— breast cancer, who had disease progression on endocrine therapy and for whom endocrine therapy was unsuitable and who had received 1-2 prior lines of chemotherapy in the inoperable/metastatic setting, were randomly assigned 1 : 1 to Dato-DXd (6 mg/kg every 3 weeks) or ICC (eribulin/capecitabine/vinorelbine/gemcitabine). Dual primary endpoints were PFS by BICR and OS. Results Overall, 83 patients were enrolled in mainland China (Dato-DXd, n = 44; ICC, n = 39). PFS by BICR numerically favored Dato-DXd versus ICC [hazard ratio (HR) 0.54, 95% confidence interval (CI) 0.30-0.96, nominal P = 0.0329; median PFS: 8.1 versus 4.2 months]. OS numerically favored Dato-DXd versus ICC [HR 0.83 (95% CI 0.49-1.43), nominal P = 0.5028]. The rate of grade ≥3 treatment-related adverse events (TRAEs) was lower with Dato-DXd versus ICC (29.5% versus 58.3%). The most common TRAEs (any grade/grade 3-4) were nausea (47.7%/4.5%) and increased aspartate aminotransferase (40.9%/2.3%) with Dato-DXd, and neutropenia (grouped term, 58.3%/36.1%) and anemia (52.8%/8.3%) with ICC. With Dato-DXd, treatment-related AEs of special interest (grouped terms) oral mucositis/stomatitis and ocular surface events occurred in 43.2% and 47.7% of patients, respectively. Conclusion In this China cohort, Dato-DXd demonstrated numerically improved efficacy versus ICC and a manageable safety profile, consistent with the global population, supporting Dato-DXd as a new treatment option for Chinese patients with previously treated metastatic HR+/HER2— breast cancer.