Unmet Needs in Maintenance Therapy for Extensive Stage Small Cell Lung Cancer

Abstract

Small cell lung cancer (SCLC) is a highly aggressive malignancy and an exceptionally lethal disease; most patients present with extensive stage (ES) disease at diagnosis. Very little had changed in the treatment of ES-SCLC for decades until immune checkpoint inhibitor (ICI) therapy combined with chemotherapy followed by ICI maintenance monotherapy was added to standard treatment paradigms in 2019. Despite this important advance, high rates of relapse are still observed in patients with ES-SCLC and long-term survival rates remain low, with approximately 40% of patients proceeding to receive second-line treatment. There is an urgent need for novel treatment strategies to improve patient outcomes. In this review, we describe the rationale for maintenance therapy approaches in ES-SCLC and summarize the existing data on chemotherapy, ICIs, and other agents in the first-line maintenance setting. Predictive biomarkers, SCLC subtypes, and new therapeutics in development are discussed including lurbinectedin, antibody-drug conjugates, and T-cell engager molecules.

Keywords: Antibody-drug conjugates; DNA topoisomerases; Immune checkpoint inhibitors; PARP inhibitors; T-cell engager molecules.