Clinical Report: Safety and Effectiveness of Antibody-Drug Conjugates in NSCLC

Overview

This systematic review and meta-analysis evaluated the efficacy and safety of antibody-drug conjugates (ADCs) in patients with EGFR-mutant non-small cell lung cancer (NSCLC) after resistance to tyrosine kinase inhibitors (TKIs). The findings report a pooled objective response rate of 44.7%.

Background

Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related mortality, particularly among patients with epidermal growth factor receptor (EGFR) mutations. Resistance to EGFR-TKIs is common, leading to limited treatment options. ADCs have emerged as a potential therapeutic strategy in this challenging setting, warranting systematic evaluation of their safety and effectiveness.

Data Highlights

Key Findings

• The pooled ORR for ADCs in EGFR-mutant NSCLC after TKI failure was 44.7%.
• TROP2-targeting ADCs demonstrated a significantly higher ORR (50.6%) compared to HER3-targeting ADCs (34.2%).
• Sacituzumab tirumotecan (Sac-TMT) showed a pooled HR of 0.40 for PFS and 0.57 for OS compared to chemotherapy.
• Patritumab deruxtecan (HER3-DXd) improved PFS (HR 0.77) but did not show a mature OS benefit.
• High heterogeneity was observed across studies, particularly driven by differences in target antigens.
• Only three studies provided mature mOS data, indicating a need for further research.

Clinical Implications

The findings support the use of ADCs, particularly TROP2-directed agents, as a treatment option for patients with EGFR-mutant NSCLC following TKI resistance.

Conclusion

ADCs demonstrate antitumor activity in EGFR-mutant NSCLC after TKI resistance, with efficacy varying by target antigen.

Related Resources & Content

1. Frontiers in Oncology, 2026 -- Optimal treatment strategies for unresectable stage III EGFR-mutated non-small cell lung cancer: a systematic review and Bayesian network meta-analysis
2. The ASCO Post, 2025 -- Sacituzumab Tirumotecan Improves Survival in EGFR-Mutated NSCLC After Tyrosine Kinase Inhibitor Failure KEY POINTS
3. FDA -- FDA grants accelerated approval to datopotamab deruxtecan-dlnk for EGFR-mutated non-small cell lung cancer
4. The ASCO Post — Efficacy, Toxicity on a Par for Different Classes of Immune Checkpoint Inhibitors
5. the asco post — Sacituzumab Tirumotecan Improves Survival in EGFR-Mutated NSCLC After Tyrosine Kinase Inhibitor Failure
6. HERTHENA-Lung01, a Phase II Trial of Patritumab Deruxtecan
7. Frontiers | Efficacy and Safety of Antibody-Drug Conjugates in EGFR-Mutant Non-Small Cell Lung Cancer After Tyrosine Kinase Inhibitor Resistance
8. FDA grants accelerated approval to datopotamab deruxtecan-dlnk for EGFR-mutated non-small cell lung cancer | FDA