Antibody drugs conjugates in small-cell lung cancer: present-day status and promises

Introduction: Small-cell lung cancer (SCLC) accounts for 15% of lung cancers and is characterized by an aggressive disease course and historically poor prognosis. Although tumors in most patients respond to initial chemotherapy, relapse is nearly universal and treatment options remain limited. Antibody-drug conjugates (ADCs) have emerged as a novel therapeutic class with the potential to address this unmet need. Methods: ClinicalTrials.gov, PubMed, and their associated references and press releases were queried for the search terms “antibody-drug ­conjugates” and “SCLC.” Only English-language sources were included. Results: Multiple ADCs targeting diverse antigens have been evaluated in relapsed or refractory SCLC. Topoisomerase I inhibitor payloads have generated the most consistent activity across delta-like protein 3, TROP2, B7-H3, and SEZ6 targets, while microtubule and pyrrolobenzodiazepine-based constructs have not demonstrated durable benefit. Despite encouraging response rates, progression-free survival has remained short, reflecting intrinsic resistance, antigen heterogeneity, and toxicity-related dose limitations. Conclusion: While ADCs have generated encouraging response rates in SCLC, durability has remained limited. Future development will require optimization of payloads, linkers, and trial design to determine whether ADCs can achieve a sustained role in this disease.