TROP2-Targeted Therapy Selection and Clinical Decision-Making

Dr. Kruse addresses patient selection for TROP2-targeted ADC therapy, noting that TROP2 expression intensity does not correlate with therapeutic efficacy. The current therapeutic landscape includes datopotamab deruxtecan (Dato-DXd) and SG, each with distinct toxicity profiles. Selection decisions involve multifactorial considerations including disease progression patterns, prior progression-free survival (PFS) duration, disease location (visceral versus bone-only), and individual patient preferences regarding treatment scheduling and toxicity management.

Dr. Kang describes the complexity of modern treatment selection, characterizing current options as creating "wealth of wishes" or data overload requiring systematic decision-making approaches. When patients are candidates for multiple ADCs, Dr. Kruse emphasizes focusing on key distinguishing factors rather than detailed efficacy data, as these agents demonstrate activity across large patient populations with uniformly positive PFS and overall survival (OS) trends. The critical differentiators become toxicity profiles and scheduling considerations that impact patient adherence and quality of life.

Specific toxicity considerations include gastrointestinal effects and interstitial lung disease (ILD) with T-DXd, neutropenia and gastrointestinal toxicities with SG, and ocular toxicities plus stomatitis with datapodumab deruxtecan. Dr. Kang identifies the primary barrier as the substantial learning curve required for each agent, necessitating provider and team education on managing distinct toxicity profiles while coaching patients through side effect management to maintain therapeutic benefit. Successful implementation requires understanding available tools for toxicity mitigation and willingness to modify dosing approaches, sometimes starting lower and escalating rather than traditional oncology practices.