Immune Checkpoint Inhibitors and Chemoradiation for Limited-Stage Small Cell Lung Cancer

Limited-stage small cell lung cancer (LS-SCLC) is a potentially curable disease. However, most patients develop disease relapse shortly after definitive treatment. The landmark trials IMpower133 and CASPIAN demonstrated a survival benefit with the addition of immunotherapy to first-line platinum/etoposide for extensive-stage small cell lung cancer. Therefore, it is critical to determine whether advancements in overall survival with immunotherapy can be translated earlier into the treatment paradigm for LS-SCLC. Decades of robust preclinical research into the synergism of radiation therapy and immunotherapy set the stage for the combination of these treatment modalities. Recently published data suggests tolerability of single agent immunotherapy concurrent with chemoradiation in LS-SCLC, along with promising efficacy. However, combination immunotherapy in the consolidation setting appears too toxic, although this may be reflective of the dosing schedule rather than inherent to any combination immune checkpoint blockade. Here, we review underlying mechanisms of synergy with the combination of radiation and immunotherapy, the safety and efficacy of respective treatment modalities, and the ongoing trials that are exploring novel therapeutic approaches for LS-SCLC. Pivotal trials in LS-SCLC are ongoing and anticipated to aid in understanding efficacy and safety of immunotherapy with concurrent platinum-based chemoradiotherapy.