{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:01:04Z","timestamp":1790704864262,"version":"4.1.0"},"reference-count":35,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sichuan Provincial People\u2019s Hospital, University of Electronic Science and Technology of China","award":["Grant no. 2023QN08"],"award-info":[{"award-number":["Grant no. 2023QN08"]}],"id":[{"id":"https:\/\/ror.org\/04qr3zq92","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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\u20135.28) and OS (HR 1.52, 1.19\u20132.01). 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\u201313.16), PTN-Cap (OR 3.35, 1.24\u20138.19), and T-DM1 (OR 6.31, 3.98\u201310.32). 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\u20131.21) and T-DXd vs T-DM1 OR 1.30 (0.87\u20131.93). T-DXd had higher ILD\/pneumonitis odds than T-DM1 (OR 5.55, 2.79\u201312.16); LVD differences were unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0358540","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:27:56Z","timestamp":1790702876000},"page":"e0358540","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"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"],"prefix":"10.1371","volume":"21","author":[{"given":"Yu","family":"Xiao","sequence":"first","affiliation":[{"name":"Sichuan Academy of Social Sciences","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Fu","sequence":"additional","affiliation":[{"name":"Sichuan Provincial People\u2019s Hospital, University of Electronic Science and Technology of China","place":["Chengdu, Sichuan, China"],"department":["Department of Breast Surgery"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Li","sequence":"additional","affiliation":[{"name":"Sichuan Provincial People\u2019s Hospital, University of Electronic Science and Technology of China","place":["Chengdu, Sichuan, China"],"department":["Department of Breast Surgery"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8129-8235","authenticated-orcid":true,"given":"Gang","family":"Hu","sequence":"additional","affiliation":[{"name":"Sichuan Provincial People\u2019s Hospital, University of Electronic Science and Technology of China","place":["Chengdu, Sichuan, China"],"department":["Department of Breast 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