Pulmonary Toxicities of Antibody-Drug Conjugates in Small Cell and Non-Small Cell Lung Cancer: A Systematic Review and Meta-analysis
In brief
One in three lung cancer patients on ADCs get pulmonary side effects
A meta-analysis of 24 trials (4,048 patients) found that 31% experienced any-grade lung toxicity and 7% had severe (grade at least 3) events, with pneumonitis/ILD occurring in 8% (2.8% severe). Toxicity was higher in small-cell disease (52% vs 23% in NSCLC) but pneumonitis was more common in NSCLC. Clinicians should monitor closely and weigh these risks when selecting ADC therapy.
- Journal
- Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer (Q1)
- Published
- 31 August 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Rodrigo Paredes de la Fuente, Roberto Borea, Diego Enrico, Katherine Santana, Lexi Weintraub, William He, et al.
- PMID
- 42674256
- DOI
- 10.1016/j.jtho.2026.104177
Why clinicians should know about it
- Picked for Pulmonary and Respiratory Medicine (top studies of the week, 6 September 2026): Pulmonary toxicities of antibody-drug conjugates in small cell and non-small
- Picked for Oncology and Radiation Oncology (top studies of the week, 6 September 2026): Meta‑analysis of pulmonary toxicities of ADCs in lung cancer
- Picked for Radiation Oncology (top studies of the week, 6 September 2026): Ranked by evidence level and journal quartile
Abstract
BACKGROUND: Antibody-drug conjugates (ADCs) are increasingly used in the treatment of small cell (SCLC) and non-small cell lung cancer (NSCLC). Despite their targeted design, clinically significant 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 to evaluate differences by tumor type and drug design features. METHODS: We performed a PRISMA-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 4,048 patients and 2,855 treated with ADCs were included. The pooled incidence of any-grade pulmonary AEs was 30.9% (95% CI, 21.5-42.3). Grade ≥3 pulmonary AEs occurred in 6.9% (95% CI, 4.6-10.3). Pneumonitis/ILD occurred in 8.0% overall, with 2.8% grade ≥3. Treatment discontinuation due to pulmonary toxicity occurred in 6.2%, and pulmonary AE-related mortality in 1.96%. Any-grade pulmonary AEs were more frequent in SCLC than in NSCLC (52.1% vs 22.5%, p = 0.005), whereas pneumonitis was more common in NSCLC than in SCLC (12.1% vs 2.8%, p < 0.001). CONCLUSIONS: Pulmonary AEs are common and clinically meaningful in lung cancer patients treated with ADCs. Pneumonitis/ILD represents the key clinically actionable toxicity, with risk influenced by tumor subtype and drug characteristics.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.