{ "abstract": "Background: HER2-positive advanced breast cancer remains challenging after trastuzumab-based therapy because available regimens differ in survival, response, and toxicity. We compared therapies used in second-line and later settings. Methods: This PRISMA-NMA-compliant review was registered with PROSPERO (CRD420251244047). PubMed, Embase, Web of Science, and CENTRAL were searched through July 24, 2026. Phase II or III randomized controlled trials after trastuzumab-based therapy were eligible. Bayesian network meta-analysis summarized PFS and OS as hazard ratios and confirmed ORR and safety outcomes as odds ratios. Random-effects models were used where heterogeneity was estimable; fixed-effect Bayesian models were used for the sparse SAE and ILD/pneumonitis networks. DoR was analyzed exploratorily using a fixed-effect Bayesian normal model after prespecified conversion of arm-level summary statistics; TTP was not quantitatively synthesized when the required summary measures were unavailable or clinically non-equivalent. Results: Sixteen reports representing seven independent randomized trial families and 3,339 unique randomized participants were included. Relative to T-DXd, T-DM1 had less favorable PFS (HR 3.30, 95% CrI 2.06–5.28) and OS (HR 1.52, 1.19–2.01). However, T-DXd was not represented in the second-line-only OS network or the Asia-dominant PFS/OS networks; therefore, its survival ranking reflects evidence primarily from mixed-line, non-Asia-dominant trials. T-DXd produced higher confirmed ORR than Lap-Cap (OR 7.43, 3.80–13.16), PTN-Cap (OR 3.35, 1.24–8.19), and T-DM1 (OR 6.31, 3.98–10.32). DoR showed no clear between-treatment difference in the EMILIA/NALA network, and TTP could not be quantitatively synthesized. Any-grade AE estimates did not indicate a safety advantage for T-DXd. SAE comparisons were also inconclusive: T-DM1 vs Lap-Cap OR 0.90 (0.67–1.21) and T-DXd vs T-DM1 OR 1.30 (0.87–1.93). T-DXd had higher ILD/pneumonitis odds than T-DM1 (OR 5.55, 2.79–12.16); LVD differences were unclear. Conclusion: Within the connected overall networks, T-DXd showed a favorable survival profile and the highest confirmed ORR, although its survival ranking was not estimable in the second-line-only OS or Asia-dominant survival networks. Its increased ILD/pneumonitis risk relative to T-DM1 is clinically important. Indirect survival comparisons and sparse safety networks require cautious interpretation.", "abstract_shown": true, "affiliations": [ "Sichuan Academy of Social Sciences, Chengdu, Sichuan, China", "Department of Breast Surgery, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China" ], "article_type": "Research Article", "arxiv": null, "author_total": 4, "authors": [ { "affs": [ 0 ], "name": "Yu Xiao" }, { "affs": [ 1 ], "name": "Jing Fu" }, { "name": "Juan Li" }, { "name": "Gang Hu" } ], "bibtex": "https://research.draconitic.com/paper/8k8ptveak4d0c.bib", "cited_by": 0, "doi": "10.1371/journal.pone.0358540", "fulltext_url": null, "id": "8k8ptveak4d0c", "issns": [ "1932-6203" ], "landing_url": "https://doi.org/10.1371/journal.pone.0358540", "language": null, "licence": "CC-BY-4.0", "licence_label": "CC BY 4.0", "licence_source": "journal", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "openalex", "2730|HER2/EGFR in Cancer Research" ], [ "plos", "/Biology and life sciences/Toxicology/Toxicity" ], [ "plos", "/Computer and information sciences/Network analysis" ], [ "plos", "/Medicine and health sciences/Epidemiology/Medical risk factors/Cancer risk factors" ], [ "plos", "/Medicine and health sciences/Neurology/Neurological tumors/Brain metastasis" ], [ "plos", "/Medicine and health sciences/Oncology/Cancer risk factors" ], [ "plos", "/Medicine and health sciences/Oncology/Cancer treatment" ], [ "plos", "/Medicine and health sciences/Oncology/Cancers and neoplasms/Breast tumors/Breast cancer" ], [ "plos", "/Medicine and health sciences/Oncology/Cancers and neoplasms/Neurological tumors/Brain metastasis" ], [ "plos", "/Medicine and health sciences/Pathology and laboratory medicine/Toxicology/Toxicity" ], [ "plos", "/Physical sciences/Mathematics/Statistics/Statistical methods/Metaanalysis" ], [ "plos", "/Research and analysis methods/Mathematical and statistical techniques/Statistical methods/Metaanalysis" ], [ "plos", "/Research and analysis methods/Research design/Clinical research design/Adverse events" ] ], "openalex": "W7214710757", "pdf_url": "https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0358540&type=printable", "pmcid": null, "pmid": null, "published": "2026-09-29", "publisher": "Public Library of Science", "ris": "https://research.draconitic.com/paper/8k8ptveak4d0c.ris", "sources": [ { "first_seen": "2026-10-30T12:17:37Z", "native_id": "10.1371/journal.pone.0358540", "source": "plos", "url": "https://doi.org/10.1371/journal.pone.0358540" } ], "subjects": [ { "field": "mathematics", "origin": "plos:statistical methods", "subfield": "statistics" }, { "field": "medicine", "origin": "plos:oncology", "subfield": "oncology" }, { "field": "medicine", "origin": "plos:toxicology", "subfield": "pharmacology-toxicology" } ], "title": "Efficacy and safety of T-DXd versus Other HER2-targeted therapies in second-line and later settings for HER2-positive metastatic breast cancer: A Bayesian network meta-analysis", "title_text": "Efficacy and safety of T-DXd versus Other HER2-targeted therapies in second-line and later settings for HER2-positive metastatic breast cancer: A Bayesian network meta-analysis", "type": "peer-reviewed", "updated_at": "2026-10-30T12:17:37Z", "url": "https://research.draconitic.com/paper/8k8ptveak4d0c", "venue": "PLOS One", "versions": [] }