Choosing Between Anti-TROP2 ADCs in Advanced Breast Cancer Without Head-to-Head Evidence: A Practical Evidence-Informed Decision Framework Endorsed by the Polish Society of Clinical Oncology

Background/Objectives: Antibody–drug conjugates (ADCs) targeting trophoblast cell-surface antigen 2 (TROP2), including sacituzumab govitecan (SG) and datopotamab deruxtecan (Dato-DXd), have expanded treatment options for patients with advanced breast cancer. Although both agents target TROP2, they differ in molecular design, clinical evidence, toxicity profiles, and monitoring requirements. Without head-to-head trials, their relative clinical positioning remains uncertain. This review aimed to critically assess the available evidence and develop a practical framework to support individualized treatment selection between SG and Dato-DXd. Methods: This narrative critical review used a structured literature search of PubMed/MEDLINE and targeted searches of major oncology guidelines, regulatory documents, pivotal-trial publications, conference reports when full publications were unavailable, and relevant retrospective or translational studies. The evidence cutoff was 29 September 2026. Direct randomized-trial evidence, indirect clinical inference, and expert/practical considerations were explicitly distinguished. Results: SG and Dato-DXd have both demonstrated clinically meaningful activity in advanced breast cancer, but their evidence base, toxicity patterns, and practical requirements differ. Cross-trial differences in populations, treatment lines, comparator composition, follow-up, subsequent therapy, response assessment, and safety reporting preclude valid numerical comparisons of efficacy or toxicity between the two agents. SG is characterized predominantly by hematologic and gastrointestinal toxicity, whereas Dato-DXd is associated with stomatitis, ocular toxicity, and interstitial lung disease/pneumonitis. These distinctions, together with patient-specific comorbidities, prior toxicities, prior ADC exposure, logistical considerations, and local healthcare resources, may inform individualized treatment selection when both agents are clinically appropriate. Conclusions: In the absence of direct comparative trials, treatment selection between SG and Dato-DXd should not rely on cross-trial efficacy or safety comparisons. The proposed framework separates regulatory and guideline eligibility from drug-specific safety evidence, indirect clinical inference, patient preferences, and healthcare system considerations. It is intended as evidence-informed clinical guidance rather than a validated comparative treatment selection rule and requires prospective evaluation.