Small cell lung cancer (SCLC) is an aggressive malignancy that accounts for 15% of all lung cancers. It is characterized by initial responsiveness to therapy followed by rapid disease progression that is relatively resistant to further treatment. Recently, the addition of an immune checkpoint inhibitor (ICI) to chemotherapy has improved survival in patients with advanced disease, the first advance in systemic therapy in SCLC in over 30 years.

In this review, we present an overview of SCLC with a focus on the scope of the problem and standard treatment, followed by a critical assessment of scientific rationale for immunotherapy in SCLC and the clinical trials that have been performed with ICIs in SCLC. Finally, we address ongoing hurdles for the development of ICIs in SCLC and potential avenues for further study.

Despite solid biological rationale, the results of clinical trials of ICIs in SCLC have yielded modest benefits. A small subset of patients does achieve long-term benefit, but further development of ICIs in SCLC will depend on the identification of predictive biomarkers and the design of combination regimens that take advantage of the molecular alterations that drive the immune-avoidance mechanisms and survival of SCLC cells.