Rationale for effective interventions to mitigate oral mucositis in patients being treated with TROP-2-directed antibody-drug conjugates with a topoisomerase inhibitor payload

Clinically significant oral mucositis (OM) is a frequently reported toxicity of TROP-2 directed ADCs containing a topoisomerase inhibitor payload, such as datopotamab deruxtecan (Dato-DXd). It seems likely that the mechanism underlying this important toxicity is consistent with the established biological cascade associated with other cytotoxic regimens and a consequence of the expression of TROP-2 on normal oral mucosa. Since it is probable that the biological processes underlying TROP-2 ADC induced OM are distinct from the inflammatory pathogenesis of stomatitis caused by mTOR inhibitors (mIAS), a rational interventional strategy which recognizes these different biological targets is critical for developing effective prevention and treatment.