Abstract
BACKGROUND: There are limited clinical data to compare the efficacy of trastuzumab deruxtecan (T-DXd) between the immunohistochemistry (IHC) 1+ and 2+ subgroups of human epidermal growth factor receptor 2 (HER2)-low metastatic breast cancer (MBC). This study investigated the outcomes of T-DXd across distinct IHC statuses in HER2-low MBC. METHODS: Patients with HER2-low MBC treated with T-DXd from June 2022 to December 2023 at The Fifth Medical Centre of Chinese PLA General Hospital were enrolled. The IHC status of patients was defined by the higher IHC score between the primary and metastatic lesions. The primary study endpoint was progression-free survival (PFS), and the secondary endpoint was safety. RESULTS: Among the 70 patients, the IHC 1+ group comprised 37 patients, and the IHC 2+ group included 33 patients. Thirty-three (47.1%) patients had received ≥3 lines of chemotherapy before T-DXd treatment. The median initial T-DXd dose was 4.6 mg/kg [interquartile range (IQR): 3.7-5.3 mg/kg] every 3 weeks. A statistically significant difference in PFS was found between the IHC 1+ and 2+ groups in both univariate and multivariate analyses (median PFS: 3 vs. 5 months; adjusted hazard ratio: 0.51, 95% confidence interval: 0.28-0.95, P=0.03). The multivariate analysis also indicated that intensive prior chemotherapy and insufficient initial T-DXd doses might negatively impact the efficacy of T-DXd. The safety analysis showed similar profiles between the IHC 1+ and 2+ groups. CONCLUSIONS: In real-world treatment scenarios, HER2-low MBC patients with higher IHC scores are more likely to benefit from T-DXd, regardless of whether the scores are detected from primary or metastatic lesions.