The efficacy and safety of datopotamab deruxtecan (Dato-DXd) in advanced solid tumors: a systematic review and
Jie Huang1, Ting Huang2, Junhua Guo2
1Hangzhou TCM Hospital of Zhejiang Chinese Medical University (Hangzhou Hospital of Traditional Chinese Medicine), Hangzhou, 310007, Zhejiang, China.
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.
Insights
Datopotamab deruxtecan (Dato-DXd) shows promising efficacy in advanced solid tumors like breast cancer and NSCLC, with a manageable safety profile. Further randomized trials are needed for widespread clinical adoption.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- TROP-2 is a cell surface protein overexpressed in various solid tumors, presenting a therapeutic target.
- Datopotamab deruxtecan (Dato-DXd) is an antibody-drug conjugate targeting TROP-2, recently approved for HR+, HER2- metastatic breast cancer.
- Preclinical and early clinical data suggest Dato-DXd's potential in treating advanced solid tumors.
Purpose of the Study:
- To conduct a meta-analysis evaluating the efficacy and safety of Dato-DXd in patients with advanced solid tumors.
- To synthesize available clinical evidence to provide a comprehensive assessment of Dato-DXd's therapeutic value.
- To inform clinical practice and future research directions regarding Dato-DXd treatment.
Main Methods:
- Systematic literature search of PubMed, Web of Science, EMBASE, and Cochrane Library up to February 18, 2025.
- Inclusion of six studies with 1,166 patients receiving Dato-DXd monotherapy for non-small cell lung cancer or breast cancer.
- Quantitative synthesis of primary outcomes (ORR, DCR) and secondary outcomes (PFS, OS, TRAEs).
Main Results:
- Pooled overall response rate (ORR) was 30.0%, and disease control rate (DCR) was 76.9%.
- Median progression-free survival (PFS) was 5.56 months, and overall survival (OS) was 12.46 months.
- Common treatment-related adverse events (TRAEs) included stomatitis (55.1%), nausea (49.4%), and alopecia (38.5%). Interstitial lung disease (ILD) occurred in 5.2% of patients.
Conclusions:
- Dato-DXd exhibits encouraging antitumor activity and a manageable safety profile in advanced breast cancer and NSCLC.
- The meta-analysis provides a valuable evidence base, but current data are mainly from early-phase, single-arm studies.
- Large-scale randomized controlled trials are essential to confirm these findings and guide widespread clinical adoption.
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