---
title: "T-DXd vs Other HER2-targeted Therapies in Later-Line HER2+ Metastatic Breast Cancer: Bayesian NMA"
id: "pubmed-42809558"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42809558"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42809558/"
doi: "10.1371/journal.pone.0358540"
published_at: "2026-09-29T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# T-DXd vs Other HER2-targeted Therapies in Later-Line HER2+ Metastatic Breast Cancer: Bayesian NMA
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42809558
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42809558/)
- **DOI:** [10.1371/journal.pone.0358540](https://doi.org/10.1371%2Fjournal.pone.0358540)
- **Published At:** 2026-09-29T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- This study is a PROSPERO-registered, PRISMA-NMA-compliant Bayesian network meta-analysis comparing second-line and later HER2-targeted regimens after trastuzumab-based therapy for HER2-positive metastatic breast cancer. - Databases (PubMed, Embase, Web of Science, CENTRAL) were searched through July 24, 2026 for Phase II/III randomized trials; 16 reports representing seven trial families and 3,339 randomized participants were included. - Primary efficacy outcomes synthesized were **progression-free survival (PFS)** and **overall survival (OS)** (hazard ratios); confirmed **objective response rate (ORR)** and safety outcomes were summarized as odds ratios. - Relative to **T-DXd**, **T-DM1** showed worse PFS (HR 3.30, 95% CrI 2.06–5.28) and worse OS (HR 1.52, 95% CrI 1.19–2.01). - **T-DXd** produced higher confirmed **ORR** versus Lap-Cap (OR 7.43, 95% CrI 3.80–13.16), PTN-Cap (OR 3.35, 1.24–8.19), and T-DM1 (OR 6.31, 3.98–10.32). - Durations of response (DoR) showed no clear between-treatment difference in the EMILIA/NALA network; time to progression (TTP) could not be quantitatively synthesized. - Any-grade adverse event estimates did not show a clear safety advantage for **T-DXd**. Serious adverse event (SAE) comparisons were inconclusive: T-DM1 vs Lap-Cap OR 0.90 (0.67–1.21); 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, 95% CrI 2.79–12.16); left ventricular dysfunction (LVD) differences were unclear. - The authors caution that **T-DXd** survival ranking was not estimable in second-line-only OS or Asia-dominant networks, so survival findings rely on mixed-line, non–Asia-dominant evidence and sparse safety networks require cautious interpretation. - No competing interests were declared by the authors. The article is open access (PLoS One, 2026).
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Affiliations Expand ### Affiliations * 1 Sichuan Academy of Social Sciences, Chengdu, Sichuan, China. * 2 Department of Breast Surgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China. * PMID: **42809558** * DOI: [ 10.1371/journal.pone.0358540 ](https://doi.org/10.1371/journal.pone.0358540) Item in Clipboard # 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 Yu Xiao et al. PLoS One. 2026. Show details Display options Display options Format Abstract PubMed PMID PLoS One Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22PLoS+One%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22PLoS+One%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42809558/) . 2026 Sep 29;21(9):e0358540. doi: 10.1371/journal.pone.0358540. eCollection 2026. ### Authors [Yu Xiao](https://pubmed.ncbi.nlm.nih.gov/?term=Xiao+Y&cauthor_id=42809558)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42809558/#short-view-affiliation-1 "Sichuan Academy of Social Sciences, Chengdu, Sichuan, China."), [Jing Fu](https://pubmed.ncbi.nlm.nih.gov/?term=Fu+J&cauthor_id=42809558)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42809558/#short-view-affiliation-2 "Department of Breast Surgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China."), [Juan Li](https://pubmed.ncbi.nlm.nih.gov/?term=Li+J&cauthor_id=42809558)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42809558/#short-view-affiliation-2 "Department of Breast Surgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China."), [Gang Hu](https://pubmed.ncbi.nlm.nih.gov/?term=Hu+G&cauthor_id=42809558)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42809558/#short-view-affiliation-2 "Department of Breast Surgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.") ### Affiliations * 1 Sichuan Academy of Social Sciences, Chengdu, Sichuan, China. * 2 Department of Breast Surgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China. * PMID: **42809558** * DOI: [ 10.1371/journal.pone.0358540 ](https://doi.org/10.1371/journal.pone.0358540) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID Linked Discoveries ## 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. Copyright: © 2026 Xiao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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