Lung cancer (Amsterdam, Netherlands) · 2026
Systemic and intracranial activity of antibody-drug conjugates in patients with non-small cell lung cancer and brain metastases: A systematic review and meta-analysis.
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Zhou Susu, Tan Jiayi, Patel Vishw, Kishi Noriko, Akhtar Komal, Benjamin Sam, Homsi Jade, Tsao Che-Kai
Аннотация
INTRODUCTION: Brain metastases (BM) remain a major clinical challenge in patients with non-small cell lung cancer (NSCLC). Although antibody-drug conjugates (ADCs) have emerged as important treatment options for advanced NSCLC, their efficacy in patients with BM remains uncertain because of concerns regarding blood-brain barrier penetration and the underrepresentation of patients with BM in clinical trials.
METHODS: A systematic literature search was conducted to identify studies evaluating ADCs in patients with NSCLC and BM. PubMed, Embase, the Cochrane Library, Web of Science, and major conference proceedings were searched. Outcomes included systemic and intracranial (IC) objective response rates (ORR), disease control rate (DCR), and grade ≥3 adverse events (AEs).
RESULTS: A total of 13 studies comprising 3,191 patients were included, of whom 905 had BM. The pooled systemic ORR was 40% (95% confidence interval [CI]: 30-52%), with a systemic DCR of 77%. ADCs achieved an IC-ORR of 33% (95% CI: 25-43%) and an IC-DCR of 78%. HER2-targeted ADCs showed substantial activity (systemic ORR: 54%; IC-ORR: 44%), while TROP-2- and HER3-targeted ADCs also showed promising activity. No significant difference in systemic ORR was observed between patients with and without BM (pooled odds ratio, 1.00; 95% CI, 0.67-1.49; p = 1.00).
CONCLUSIONS: ADCs demonstrated clinically meaningful systemic and intracranial activity in patients with NSCLC and BM, with no significant difference in systemic ORR by BM status. These findings support ADCs as a promising therapeutic option for this underserved population.
METHODS: A systematic literature search was conducted to identify studies evaluating ADCs in patients with NSCLC and BM. PubMed, Embase, the Cochrane Library, Web of Science, and major conference proceedings were searched. Outcomes included systemic and intracranial (IC) objective response rates (ORR), disease control rate (DCR), and grade ≥3 adverse events (AEs).
RESULTS: A total of 13 studies comprising 3,191 patients were included, of whom 905 had BM. The pooled systemic ORR was 40% (95% confidence interval [CI]: 30-52%), with a systemic DCR of 77%. ADCs achieved an IC-ORR of 33% (95% CI: 25-43%) and an IC-DCR of 78%. HER2-targeted ADCs showed substantial activity (systemic ORR: 54%; IC-ORR: 44%), while TROP-2- and HER3-targeted ADCs also showed promising activity. No significant difference in systemic ORR was observed between patients with and without BM (pooled odds ratio, 1.00; 95% CI, 0.67-1.49; p = 1.00).
CONCLUSIONS: ADCs demonstrated clinically meaningful systemic and intracranial activity in patients with NSCLC and BM, with no significant difference in systemic ORR by BM status. These findings support ADCs as a promising therapeutic option for this underserved population.