Emerging landscape of antibody-drug conjugates in lung cancer: a clinical review.

Abstract

Lung cancer is a heterogeneous disease, and while targeted therapies and immunotherapies have improved patient outcomes, 5-year overall survival remains poor at approximately 20%. Antibody-drug conjugates (ADCs) target tumors using a targeted antibody that delivers a cytotoxic payload with clinically proven antitumor activity, and over a dozen ADCs are under consideration for solid tumors. Recent clinical trial data in metastatic non-small cell lung cancer have led to FDA approval of three ADCs: trastuzumab deruxtecan for patients with human epidermal growth factor receptor 2-mutated disease, telisotuzumab vedotin for MET-overexpressing tumors, and datopotamab deruxtecan for patients with epidermal growth factor receptor-mutated disease. In this article, we review the trajectory of individual ADC targets in lung cancer, describe the latest clinical trial results, and discuss future innovations in ADC therapies and potential mechanisms of resistance.