<p>PRISMA 2020 checklist.</p>

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.</p> <p>Results</p><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 2.06–5.28) 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.</p> <p>Conclusion</p><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.</p></div>