The efficacy and safety of datopotamab deruxtecan (Dato-DXd) in advanced solid tumors: a systematic review and meta-analysis.

BACKGROUND: The cell surface protein TROP-2 is overexpressed in various solid tumors, making it an attractive therapeutic target. Datopotamab deruxtecan (Dato-DXd) is a novel antibody-drug conjugate (ADC) designed to selectively deliver cytotoxic agents to TROP-2-expressing cancer cells. It has recently been approved for treating unresectable or metastatic hormone receptor-positive, HER2-negative breast cancer. While preclinical and early phase clinical trials have shown promising efficacy, this meta-analysis aims to provide a comprehensive evaluation of the efficacy and safety of Dato-DXd in patients with advanced solid tumors by synthesizing the available clinical evidence. METHODS: We systematically searched PubMed, Web of Science, EMBASE, and the Cochrane Library for studies published up to February 18, 2025, that investigated Dato-DXd in advanced solid tumors. The primary outcomes were the overall response rate (ORR) and disease control rate (DCR). Secondary outcomes included progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs). Data were extracted and pooled for quantitative synthesis. RESULTS: Six studies involving 1,166 patients with non-small cell lung cancer (NSCLC) or breast cancer who received Dato-DXd monotherapy were included. The pooled ORR was 30.0%, and the pooled DCR was 76.9%. The median PFS and OS were 5.56 months and 12.46 months, respectively. The most common TRAEs were stomatitis (all grades: 55.1%, grade ≥ 3: 6.8%), nausea (all grades: 49.4%, grade ≥ 3: 1.3%), and alopecia (all grades: 38.5%, grade ≥ 3: 0.0%). Interstitial lung disease (ILD), a critical adverse event of interest, occurred in 5.2% of patients (all grades) and 1.7% (grade ≥ 3). CONCLUSIONS: Dato-DXd demonstrates encouraging antitumor activity and a manageable safety profile in several advanced solid tumors, particularly breast cancer and NSCLC. This synthesis provides a valuable evidence base to guide clinical practice and future trial design. However, as the current evidence is predominantly from early phase and single-arm studies, confirmation through large-scale randomized controlled trials is necessary before Dato-DXd can be widely adopted in clinical practice.