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Peer-reviewedCC BYCancers

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.

7 affiliations
  1. 1Department of Oncology, Jagiellonian University-Medical College, 31-501 Krakow, Poland.
  2. 2Department of Oncology, University Hospital, 30-688 Krakow, Poland.
  3. 3Department of Breast Cancer and Reconstructive Surgery, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland.
  4. 4Scientific Students' Society, Jagiellonian University-Medical College, 31-008 Krakow, Poland.
  5. 5Department of Oncology, Institute of Medical Sciences, University of Opole, 45-052 Opole, Poland.
  6. 6Department of Clinical Oncology, Tadeusz Koszarowski Cancer Center in Opole, 45-061 Opole, Poland.
  7. 7Department of Lung and Chest Tumors, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland.

Abstract

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.

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BibTeX
@article{wysocki2026choosing,
  title = {{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.}},
  author = {Piotr J Wysocki and Katarzyna Pogoda and Ewa Wysocka and Barbara Radecka and Maciej Krzakowski},
  journal = {Cancers},
  year = {2026},
  month = oct,
  doi = {10.3390/cancers18193227},
  url = {https://europepmc.org/article/MED/42882921},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - 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.
AU  - Piotr J Wysocki
AU  - Katarzyna Pogoda
AU  - Ewa Wysocka
AU  - Barbara Radecka
AU  - Maciej Krzakowski
PY  - 2026
DA  - 2026/10/07
JO  - Cancers
DO  - 10.3390/cancers18193227
UR  - https://europepmc.org/article/MED/42882921
AB  - 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.
SN  - 2072-6694
ER  -