Second-Line Treatment Options for Small-Cell Lung Cancer: A Light at the End of the Tunnel

Abstract

Small-cell lung cancer (SCLC) is a subtype of lung tumor characterized by rapid growth and early metastatic dissemination. It represents approximately 15% of all diagnosed lung cancers, with an annual incidence of over 200,000 cases worldwide. At the time of initial diagnosis, approximately 75–80% of patients already have extrathoracic spread. Almost all patients with SCLC also relapse after achieving a complete response with first-line treatment. Outcomes achievable in second-line treatment are related to the length of time between completion of first-line therapy and disease progression. While first-line chemo-immunotherapy remains the standard of care for initial management, the role of second-line treatment strategies in SCLC has been a topic of significant research and discussion. Second-line treatment options are limited and the results are still disappointing. Several molecules are currently being studied in lines following the first, using immunological targets and cell cycle checkpoints. Among these, particular interest has been placed on anti-PD-1 (programmed cell death-1 protein) and anti-PD-L1 (programmed cell death-ligand 1) monoclonal antibodies, and DLL3 (Delta-like ligand 3), which are being evaluated alone or in combination. Tarlatamab is a novel promising therapeutic antibody currently under investigation for its potential use in previously treated SCLC patients. This mini-review will explore the current state of second-line treatment options for SCLC, their clinical efficacy, and future directions.