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
- 1Sichuan Academy of Social Sciences, Chengdu, Sichuan, China
- 2Department of Breast Surgery, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
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.
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BibTeX
@article{xiao2026efficacy,
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}},
author = {Yu Xiao and Jing Fu and Juan Li and Gang Hu},
journal = {PLOS One},
year = {2026},
month = sep,
doi = {10.1371/journal.pone.0358540},
url = {https://doi.org/10.1371/journal.pone.0358540},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - 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
AU - Yu Xiao
AU - Jing Fu
AU - Juan Li
AU - Gang Hu
PY - 2026
DA - 2026/09/29
JO - PLOS One
DO - 10.1371/journal.pone.0358540
UR - https://doi.org/10.1371/journal.pone.0358540
AB - 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.
SN - 1932-6203
ER -