Efficacy and safety of antibody-drug conjugates in advanced small cell lung cancer: a systematic review and single-arm meta-analysis of prospective clinical trials.

Abstract

Background: Antibody-drug conjugates (ADCs) are being evaluated in advanced small cell lung cancer (SCLC), but the available trials include different targets, constructs, doses, and treatment settings. We aimed to determine the overall range of reported activity and safety while clarifying whether the evidence supports a clinically uniform ADC class effect.

Methods: PubMed/MEDLINE, Embase, Web of Science, the Cochrane Central Register of Controlled Trials (CENTRAL), clinical-trial registries, and major oncology conference proceedings were searched from inception through July 31, 2026. Eligibility was restricted to reports with sufficient methodological and outcome information available in English; study country, recruitment region, investigator nationality, and participant ethnicity were not exclusion criteria. Prospective phase I-III studies of ADC monotherapy in adults with advanced, extensive-stage, relapsed, or refractory SCLC were eligible; no comparator was required, and only the ADC arm of comparative trials contributed to the single-arm synthesis. Outcomes were objective response rate (ORR), disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and clinically important safety events. Randomized trials were assessed using the Cochrane risk-of-bias tool and non-comparative studies using the Methodological Index for Non-Randomized Studies (MINORS). Random-effects models were used, with subgroup and sensitivity analyses.

Results: Eighteen prospective studies comprising 20 analytic cohorts and 2,246 patients were included: 12 phase I/Ib/I-II studies, three phase II studies, and three phase III studies. The pooled ORR was 34.38% [95% confidence interval (CI): 24.96-44.43%; I²=95.3%], and the pooled DCR was 77.50% (95% CI: 67.98-85.81%; I²=94.7%). The pooled median DOR, PFS, and OS were 4.99 months (95% CI: 4.24-5.86; I²=77.2%), 4.36 months (95% CI: 3.87-4.92; I²=84.8%), and 7.48 months (95% CI: 6.15-9.10; I²=92.6%), respectively. Subgroup analyses by intervention and target indicated substantial clinical and statistical heterogeneity. Safety was summarized by individual agent, dose, and source population because adverse-event definitions and denominators were not sufficiently comparable; the predominant hematologic, gastrointestinal, pulmonary, and neurologic signals varied among products. Cochrane risk-of-bias judgments were predominantly low risk, with selected domains rated unclear or high risk. MINORS scores ranged from 11 to 15 of 16, with recurrent limitations in consecutive enrollment, blinded endpoint assessment, follow-up reporting, and prospective sample-size calculation.

Conclusions: ADC-based therapy shows antitumor activity in advanced SCLC, but substantial clinical and pharmacological heterogeneity limits the interpretation of pooled single-arm estimates. Agent-specific randomized trials with standardized efficacy, safety, and biomarker reporting are needed.