Comparative Safety Profiles of Sacituzumab Govitecan and Datopotamab Deruxtecan: A Real-World Pharmacovigilance Study.

Background

Sacituzumab govitecan (SG) and datopotamab deruxtecan (Dato-DXd) are TROP2-directed antibody-drug conjugates with topoisomerase I inhibitor payloads but distinct recognized adverse-event profiles. Comparative reporting patterns for these agents remain incompletely characterized.

Methods

We analyzed a case-level line listing downloaded from the U.S. Food and Drug Administration (FDA) Adverse Event Monitoring System (AEMS; formerly the FDA Adverse Event Reporting System [FAERS]) Public Dashboard on 7 July 2026. Reports listing SG or Dato-DXd among suspect product names or active ingredients were assigned mutually exclusively. Prespecified toxicity phenotypes and individual MedDRA Preferred Terms (PTs) were compared using reporting proportions, comparative reporting odds ratios (RORs), false-discovery-rate correction, and multivariable logistic regression. A breast cancer-restricted analysis with crude RORs and 95% CIs was also performed.

Results

The cohort comprised 6368 distinct Case IDs (SG, 5714; Dato-DXd, 654). Compared with SG, Dato-DXd reports were enriched for mucositis/stomatitis (18.3% vs. 1.3%; ROR, 17.61; adjusted reporting odds ratio [aROR], 20.04) and ocular toxicity (10.9% vs. 0.9%; ROR, 13.26; aROR, 13.98). The aRORs for Dato-DXd versus SG were 0.11 for hematologic cytopenia, 0.12 for neutropenia/febrile neutropenia, 0.11 for diarrhea/colitis, and 0.57 for infection/sepsis. Exact interstitial lung disease/pneumonitis showed reporting enrichment with Dato-DXd in the unadjusted analysis (ROR, 3.12), but the comparative reporting association was attenuated after adjustment (aROR, 1.44; 95% CI, 0.87-2.39). Overall gastrointestinal reporting was similar, and the breast cancer-restricted crude RORs were directionally consistent with the full-cohort comparisons.

Conclusions

SG and Dato-DXd showed distinct adverse-event reporting profiles. SG reports were characterized by relative enrichment of hematologic and diarrheal events, whereas Dato-DXd reports were enriched for mucosal and ocular events. These findings are hypothesis-generating reporting comparisons and should not be interpreted as incidence estimates, causal associations, or conventional head-to-head safety estimates.