Front Line Applications and Future Directions of Immunotherapy in Small-Cell Lung Cancer

Simple Summary Small-cell lung cancer (SCLC) is an aggressive malignancy with a high risk of recurrence and poor prognosis despite aggressive treatment. The use of immunotherapy has revolutionized the therapeutic landscape of SCLC with the introduction of novel, effective treatment options. Immune checkpoint inhibitors (ICIs) are the primary type of immunotherapy that have been used, first in the extensive-stage setting and now under investigation in the limited-stage setting. Here, we review the use of ICIs in SCLC as well as other emerging immunotherapy strategies. After being stagnant for decades, there has finally been a paradigm shift in the treatment of small-cell lung cancer (SCLC) with the emergence and application of immune checkpoint inhibitors (ICIs). Multiple trials of first-line ICI-chemotherapy combinations have demonstrated survival benefit compared to chemotherapy alone in patients with extensive-stage SCLC, establishing this as the new standard of care. ICIs are now being applied in the potentially curative limited-stage setting, actively being investigated as concurrent treatment with chemoradiation and as adjuvant treatment following completion of chemoradiation. This review highlights the evidence behind the practice-changing addition of ICIs in the first-line setting of extensive-stage SCLC, the potentially practice-changing immunotherapy trials that are currently underway in the limited-stage setting, and alternate immunotherapeutic strategies being studied in the treatment of SCLC.