Efficacy and safety of B7-H3-targeted antibody-drug conjugates in previously treated small cell lung cancer: a systematic review and meta-analysis with a contextual comparison to topotecan.

B7-H3-targeted antibody-drug conjugates (B7-H3-targeted ADCs) have shown promising antitumor effects in patients with previously treated small cell lung cancer (SCLC), yet the available evidence on their efficacy and safety has not been systematically synthesized. This study aimed to systematically evaluate the efficacy and safety of B7-H3-targeted ADCs and contextualize their clinical outcomes against standard-dose intravenous topotecan. This systematic review and meta-analysis was conducted in accordance with PRISMA guidelines. PubMed, Embase, and the Cochrane Library were searched from inception to July 7, 2026. Prospective single-arm studies of B7-H3-targeted ADCs and randomized controlled trials (RCTs) with separately extractable topotecan arms were included. Study quality was assessed using the Newcastle-Ottawa Scale and Cochrane RoB 2 tool. Random-effects models were used to pool efficacy and safety outcomes. Evidence from the two treatment groups was synthesized separately. Results for B7-H3-targeted ADCs were descriptive, whereas topotecan was used solely as an external clinical benchmark; therefore, the contextual comparison should not be interpreted as a direct comparative estimate. Ten studies were included, comprising four prospective single-arm studies of B7-H3-targeted ADCs and six RCTs with eligible topotecan arms. For B7-H3-targeted ADCs, the pooled objective response rate (ORR) and disease control rate (DCR) were 54% (95% CI: 46%-62%) and 89% (95% CI: 85%-92%), respectively. The pooled median duration of response and median progression-free survival were both 5.6 months (95% CI: 4.8-6.4 and 4.7-6.5 months, respectively). The pooled incidences of any-grade and grade ≥3 treatment-related adverse events were 99% (95% CI: 98%-100%) and 61% (95% CI: 55%-67%), respectively. In the exploratory contextual analysis, ifinatamab deruxtecan achieved an ORR of 49% (95% CI: 41%-57%) and a DCR of 87% (95% CI: 81%-92%), whereas the corresponding estimates for topotecan were 18% (95% CI: 15%-22%) and 65% (95% CI: 61%-69%). Overall, the exploratory comparison showed numerically higher efficacy estimates and selected safety differences favoring ifinatamab deruxtecan compared with topotecan. B7-H3-targeted ADCs show promising clinical activity in patients with previously treated SCLC. In the exploratory contextual comparison, ifinatamab deruxtecan showed numerically favorable efficacy estimates and selected safety outcomes compared with topotecan. https://www.crd.york.ac.uk/PROSPERO, identifier CRD420251237597, version 3.0.