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Published on: September 25, 2018
Pulmonary Toxicities of Antibody-Drug Conjugates in SCLC and NSCLC: A Systematic Review and Meta-analysis
Rodrigo Paredes de la Fuente1, Roberto Borea2, Diego Enrico3
1Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York; Division of Hematology and Medical Oncology, The Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, New York.
Background:
Antibody-drug conjugates (ADCs) are increasingly used in the treatment of SCLC and NSCLC. Despite their targeted design, clinically considerable pulmonary adverse events (AEs) have been reported, but the incidence and toxicity profile in lung cancer remain incompletely defined. We aimed to quantify the incidence and severity of pulmonary AEs associated with ADCs and evaluate differences by tumor type and drug-design features.
Methods:
We performed a Preferred Reporting Items for Systematic Reviews and Meta-Analyses-guided systematic review and meta-analysis registered in PROSPERO (CRD42024543340). MEDLINE (Ovid), Embase (Ovid), and Cochrane CENTRAL were searched for studies published through January 2, 2025. Eligible studies included randomized controlled trials and prospective single-arm clinical trials evaluating ADCs in patients with SCLC or NSCLC. The primary outcome was the pooled incidence of pulmonary AEs using random-effects models.
Results:
Twenty-four studies comprising 4048 patients, of whom 2855 were treated with ADCs, were included. The pooled incidence of any-grade pulmonary AEs was 30.9% (95% confidence interval: 21.5%-42.3%). Grade 3 or higher pulmonary AEs occurred in 6.9% (95% confidence interval: 4.6%-10.3%). Pneumonitis or interstitial lung disease occurred in 8.0% overall, with 2.8% being grade 3 or higher. Treatment discontinuation due to pulmonary toxicity occurred in 6.2%, and pulmonary AE-related mortality occurred in 1.96%. Any-grade pulmonary AEs were more frequent in SCLC than in NSCLC (52.1% versus 22.5%, p = 0.005), whereas pneumonitis was more common in NSCLC than in SCLC (12.1% versus 2.8%, p < 0.001).
Conclusions:
Pulmonary AEs are common and clinically meaningful in patients with lung cancer treated with ADCs. Pneumonitis or interstitial lung disease represents the key clinically actionable toxicity, with risk being influenced by tumor subtype and drug characteristics.
