{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T10:52:47Z","timestamp":1791370367085,"version":"4.3.1"},"reference-count":36,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Antibody\u2013drug 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.<\/jats:p>","DOI":"10.3390\/cancers18193227","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T10:13:02Z","timestamp":1791367982000},"page":"3227","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"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"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4003-5278","authenticated-orcid":false,"given":"Piotr J.","family":"Wysocki","sequence":"first","affiliation":[{"name":"Department of Oncology, Jagiellonian University\u2014Medical College, 31-501 Krakow, Poland"},{"name":"Department of Oncology, University Hospital, 30-688 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9902-711X","authenticated-orcid":false,"given":"Katarzyna","family":"Pogoda","sequence":"additional","affiliation":[{"name":"Department of Breast Cancer and Reconstructive Surgery, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa","family":"Wysocka","sequence":"additional","affiliation":[{"name":"Scientific Students\u2019 Society, Jagiellonian University\u2014Medical College, 31-008 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Radecka","sequence":"additional","affiliation":[{"name":"Department of Oncology, Institute of Medical Sciences, University of Opole, 45-052 Opole, Poland"},{"name":"Department of Clinical Oncology, Tadeusz Koszarowski Cancer Center in Opole, 45-061 Opole, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3324-0900","authenticated-orcid":false,"given":"Maciej","family":"Krzakowski","sequence":"additional","affiliation":[{"name":"Department of Lung and Chest Tumors, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1056\/NEJMoa2028485","article-title":"Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer (ASCENT)","volume":"384","author":"Bardia","year":"2021","journal-title":"N Engl. J. Med."},{"key":"ref_2","unstructured":"U.S. Food and Drug Administration (2026, September 29). FDA Approves Datopotamab Deruxtecan-Dlnk for Unresectable or Metastatic Triple-Negative Breast Cancer, Available online: https:\/\/www.fda.gov\/drugs\/resources-information-approved-drugs\/fda-approves-datopotamab-deruxtecan-dlnk-unresectable-or-metastatic-triple-negative-breast-cancer."},{"key":"ref_3","unstructured":"(2026). Datroway Approved in the EU as Only TROP2-Directed Medicine with Overall Survival Benefit for the 1st-Line Treatment of Patients with Metastatic TNBC Who Are not Candidates for Immunotherapy [Press Release], AstraZeneca. Available online: https:\/\/www.astrazeneca.com\/media-centre\/press-releases\/2026\/datroway-approved-in-eu-for-tnbc.html."},{"key":"ref_4","unstructured":"European Medicines Agency (2026). Datroway-Opinion on Variation to Marketing Authorization, European Medicines Agency. Available online: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/variation\/datroway."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4405","DOI":"10.1158\/1078-0432.CCR-25-1388","article-title":"FDA Approval Summary: Datopotamab Deruxtecan-dlnk for Treatment of Patients with Unresectable or Metastatic, HR-Positive, HER2-Negative Breast Cancer","volume":"31","author":"Royce","year":"2025","journal-title":"Clin. Cancer Res."},{"key":"ref_6","unstructured":"European Medicines Agency (2026, September 29). Datroway: EPAR-Medicine Overview. 2025. Marketing Authorisation Granted 4 April 2025. Available online: https:\/\/www.ema.europa.eu\/lt\/medicines\/human\/EPAR\/datroway."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1200\/JCO.24.00920","article-title":"Datopotamab Deruxtecan Versus Chemotherapy in Previously Treated Inoperable\/Metastatic Hormone Receptor-Positive Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer: Primary Results From TROPION-Breast01","volume":"43","author":"Bardia","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.annonc.2025.12.017","article-title":"Datopotamab deruxtecan versus chemotherapy in previously treated inoperable\/metastatic hormone receptor-positive, HER2-negative breast cancer: Final overall survival analysis of the phase III TROPION-Breast01 study","volume":"37","author":"Pistilli","year":"2026","journal-title":"Ann. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1016\/S0140-6736(23)01245-X","article-title":"Overall survival with sacituzumab govitecan in hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer (TROPiCS-02): A randomised, open-label, multicentre, phase 3 trial","volume":"402","author":"Rugo","year":"2023","journal-title":"Lancet"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1912","DOI":"10.1056\/NEJMoa2511734","article-title":"Sacituzumab govitecan in untreated, advanced triple-negative breast cancer (ASCENT-03)","volume":"393","author":"Punie","year":"2025","journal-title":"N Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1016\/j.annonc.2026.03.008","article-title":"Datopotamab deruxtecan in patients with untreated, advanced triple-negative breast cancer (TROPION-Breast02): A randomised, open-label, international, phase III trial","volume":"37","author":"Dent","year":"2026","journal-title":"Ann. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1158\/1557-3265.SABCS25-GS1-09","article-title":"Abstract GS1-09: Sacituzumab govitecan vs. chemotherapy as first therapy after endocrine therapy in HR+\/HER2\u2212 (IHC 0, 1+, 2+\/ISH\u2212) metastatic breast cancer: Primary results from ASCENT-07","volume":"32","author":"Jhaveri","year":"2026","journal-title":"Clin. Cancer Res."},{"key":"ref_13","unstructured":"U.S. Food and Drug Administration (2026, September 29). DATROWAY (Datopotamab Deruxtecan-Dlnk) Prescribing Information, Available online: https:\/\/datrowayhcp.com\/mtnbc."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1056\/NEJMoa2508959","article-title":"Sacituzumab Govitecan plus Pembrolizumab for Advanced Triple-Negative Breast Cancer (ASCENT-04\/KEYNOTE-D19)","volume":"394","author":"Tolaney","year":"2026","journal-title":"N Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2329","DOI":"10.1158\/1535-7163.MCT-21-0206","article-title":"Datopotamab Deruxtecan, a Novel TROP2-Directed Antibody-Drug Conjugate, Demonstrates Potent Antitumor Activity by Efficient Drug Delivery to Tumor Cells","volume":"20","author":"Okajima","year":"2021","journal-title":"Mol. Cancer Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1248\/cpb.c18-00744","article-title":"The Latest Research and Development into the Antibody-Drug Conjugate, [fam-] Trastuzumab Deruxtecan (DS-8201a), for HER2 Cancer Therapy","volume":"67","author":"Nakada","year":"2019","journal-title":"Chem. Pharm. Bull."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1016\/j.annonc.2026.05.707","article-title":"Metastatic breast cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","volume":"37","author":"Barrios","year":"2026","journal-title":"Ann. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e260033","DOI":"10.6004\/jnccn.2026.0033","article-title":"Breast Cancer, Version 4.2026, NCCN Clinical Practice Guidelines in Oncology","volume":"24","author":"Gradishar","year":"2026","journal-title":"J. Natl. Compr. Canc Netw."},{"key":"ref_19","first-page":"324","article-title":"AGO Recommendations for the Diagnosis and Treatment of Patients with Locally Advanced and Metastatic Breast Cancer: Update 2026","volume":"21","author":"Thill","year":"2026","journal-title":"Breast Care"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1200\/JCO.22.02807","article-title":"Chemotherapy and Targeted Therapy for Endocrine-Pretreated or Hormone Receptor\u2013Negative Metastatic Breast Cancer: ASCO Guideline Rapid Recommendation Update","volume":"41","author":"Moy","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"11","DOI":"10.21037\/tbcr-2025-1-81","article-title":"Datopotamab deruxtecan in Chinese patients with heavily pretreated advanced or metastatic triple-negative breast cancer in the phase I\/II TROPION-PanTumor02 study","volume":"7","author":"Wang","year":"2026","journal-title":"Transl. Breast Cancer Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"108330","DOI":"10.1016\/j.esmoop.2026.108330","article-title":"Datopotamab deruxtecan versus chemotherapy in previously treated inoperable\/metastatic hormone receptor-positive HER2-negative breast cancer: Safety and patient-reported outcomes from the phase III TROPION-Breast01 study","volume":"11","author":"Rugo","year":"2026","journal-title":"ESMO Open"},{"key":"ref_23","unstructured":"Gilead Sciences Inc. (2026). TRODELVY (Sacituzumab Govitecan-Hziy) U.S. Prescribing Information, Gilead Sciences, Inc.. Available online: https:\/\/www.gilead.com\/-\/media\/files\/pdfs\/medicines\/oncology\/trodelvy\/trodelvy_pi."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"100554","DOI":"10.1016\/j.esmoop.2022.100554","article-title":"Pooled analysis of drug-related interstitial lung disease and\/or pneumonitis in nine trastuzumab deruxtecan monotherapy studies","volume":"7","author":"Powell","year":"2022","journal-title":"ESMO Open"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1002\/cpt.70060","article-title":"UGT1A1 and Sacituzumab Govitecan Toxicity: A Systematic Review and Meta-Analysis","volume":"119","author":"Asiimwe","year":"2026","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1038\/s41416-024-02766-9","article-title":"Efficacy of administration sequence: Sacituzumab Govitecan and Trastuzumab Deruxtecan in HER2-low metastatic breast cancer (ADC-Low)","volume":"131","author":"Poumeaud","year":"2024","journal-title":"Br. J. Cancer"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/s41523-025-00748-5","article-title":"Multicenter retrospective cohort study of the sequential use of the antibody-drug conjugates (ADCs) trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG) in patients with HER2-low metastatic breast cancer (MBC)","volume":"11","author":"Huppert","year":"2025","journal-title":"npj Breast Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2281","DOI":"10.1200\/JCO.23.01909","article-title":"Datopotamab Deruxtecan in Advanced or Metastatic HR+\/HER2\u2212 and Triple-Negative Breast Cancer: Results from the Phase I TROPION-PanTumor01 Study","volume":"42","author":"Bardia","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1158\/1078-0432.CCR-25-3321","article-title":"Payload Diversification Overcomes Resistance and Guides Sequential Antibody-Drug Conjugate Therapy in Breast Cancer","volume":"32","author":"Rampa","year":"2026","journal-title":"Clin. Cancer Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.1158\/1078-0432.CCR-24-2771","article-title":"TOP1 Mutations and Cross-Resistance to Antibody\u2013Drug Conjugates in Patients with Metastatic Breast Cancer","volume":"31","author":"Abelman","year":"2025","journal-title":"Clin. Cancer Res."},{"key":"ref_31","unstructured":"ClinicalTrials.gov (2026, September 10). STORM: Sequencing Sacituzumab Govitecan vs. Trastuzumab Deruxtecan in HER2-Low\/TROP2-High Metastatic Breast Cancer. NCT07368543, Available online: https:\/\/clinicaltrials.gov\/study\/NCT07368543."},{"key":"ref_32","unstructured":"ClinicalTrials.gov (2026, September 10). Testing Two Different Drugs (Sacituzumab-Govitecan and Trastuzumab-Deruxtecan) Combinations Prescribed in an Alterning Pattern to Patients with Metastatic or Locally Advanced Triple-Negative Breast Cancer (ALTER). NCT07151586, Available online: https:\/\/ckb.genomenon.com\/clinicalTrial\/show?nctId=NCT07151586."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1056\/NEJMoa2203690","article-title":"Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer (DESTINY-Breast04)","volume":"387","author":"Modi","year":"2022","journal-title":"N Engl. J. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2110","DOI":"10.1056\/NEJMoa2407086","article-title":"Trastuzumab Deruxtecan after Endocrine Therapy in Metastatic Breast Cancer (DESTINY-Breast06)","volume":"391","author":"Bardia","year":"2024","journal-title":"N Engl. J. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4205","DOI":"10.1038\/s41591-025-03981-4","article-title":"Trastuzumab deruxtecan in HER2-low metastatic breast cancer: Long-term survival analysis of the randomized, phase 3 DESTINY-Breast04 trial","volume":"31","author":"Modi","year":"2025","journal-title":"Nat. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1186\/s13058-025-02094-7","article-title":"Comparison of trastuzumab deruxtecan and sacituzumab govitecan in HER2-negative metastatic breast cancer: A large real-world data analysis","volume":"27","author":"Sledge","year":"2025","journal-title":"Breast Cancer Res."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/19\/3227\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T10:16:46Z","timestamp":1791368206000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/19\/3227"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,7]]},"references-count":36,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["cancers18193227"],"URL":"https:\/\/doi.org\/10.3390\/cancers18193227","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,7]]}}}