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.