Efficacy and safety of datopotamab deruxtecan in advanced/metastatic non-small cell lung cancer patients: a systematic review and single-arm meta-analysis.

BACKGROUND

Datopotamab deruxtecan (dato-DXd), an antibody-drug conjugate (ADC) targeting trophoblast cell-surface antigen 2 (TROP2), has shown promising results in advanced/metastatic (a/m) non-small cell lung cancer (NSCLC). This systematic review and meta-analysis evaluated the efficacy and safety of dato-DXd in this population.

METHODS

A systematic search from inception until July 14, 2024 was performed on PubMed, Embase, Cochrane, the American Society of Clinical Oncology (ASCO), and the European Society for Medical Oncology (ESMO) databases for studies examining dato-DXd in patients with a/m NSCLC. Outcomes were progression-free survival (PFS) and overall survival (OS), objective response rate (ORR), disease control rate (DCR), and incidence of adverse events (AEs). Random-effect models were used for analysis.

RESULTS

Seven clinical trials involving 914 a/m NSCLC patients treated with dato-DXd were included. Most patients received dato-DXd as monotherapy (6 mg/kg Q3W). Overall, 35% [95% confidence interval (CI): 27-43%] achieved an ORR, and 78% (95% CI: 75-81%) achieved a DCR. Non-squamous histology showed numerically higher ORR (28% vs. 8%) and significantly better PFS and OS (P<0.01) than squamous histology. Median PFS and OS were 5.43 months (95% CI: 4.14-7.12) and 11.93 months (95% CI: 10.43-13.65), respectively. AEs led to dose reductions in 20% (95% CI: 17-23%) and treatment discontinuation in 22% (95% CI: 10-40%) of patients. Serious treatment-emergent AEs (TEAEs) occurred in 30% (95% CI: 19-45%). Common all-grade AEs included stomatitis (49%), nausea (48%) and alopecia (39%). Interstitial lung disease (ILD) was reported in 7% of patients, with 4% experiencing grade ≥3 events. Sensitivity analyses confirmed consistent ORR and DCR across doses.

CONCLUSIONS

Dato-DXd demonstrated notable efficacy in heavily pretreated a/m NSCLC patients, with a median PFS and OS of 5.4 and 11.9 months, respectively. The rate of AE was substantial, including treatment discontinuation in nearly one-quarter of patients. Ongoing studies on the activity and safety profile of dato-DXd in a/m NSCLC are awaited.