Rationale for Chemotherapy, Immunotherapy, and Checkpoint Blockade in SCLC: Beyond Traditional Treatment Approaches

IntroductionSmall cell lung cancer (SCLC) is an aggressive malignancy that although initially sensitive to chemo- and radiation therapy, inevitably relapses resulting in poor survival. Increasing evidence suggests that immune responses against SCLC cells make immunotherapy a viable therapeutic approach. Furthermore, preclinical data have shown that certain chemotherapeutic regimens may augment the immunotherapeutic response in SCLC. This review discusses current evidence supporting immunotherapy for SCLC, progress made, and ongoing clinical trials.MethodsWe searched PubMed and abstracts presented at recent oncology congresses for publications on the clinical benefit of immunotherapy/checkpoint blockade for treatment of SCLC.ResultsPreliminary data from ongoing clinical trials in SCLC have shown that some antiangiogenic agents, vaccines, and immunomodulators, including interferon-α and immune checkpoint blockers (i.e., anticytotoxic T-lymphocyte-associated antigen-4 [CTLA-4] antibodies) may be efficacious as single agents and in combination with standard-of-care regimens. Notably, in a phase II trial, ipilimumab—a fully human anti-CTLA-4 monoclonal antibody recently approved for treatment of unresectable or metastatic melanoma—demonstrated encouraging results when used as part of a chemoimmunotherapeutic regimen in patients with SCLC. Ipilimumab is undergoing further investigation in this population.ConclusionsTreatment options for SCLC are limited and prognosis poor, emphasizing the need for novel treatments. Although current strategies successfully induce a response, the response is not durable. Evidence of an immune response in SCLC and a better understanding of the immunosuppressive tumor environment support the combinatorial use of immunomodulators, such as ipilimumab, with traditional chemotherapy regimens to improve patient outcomes and potentially sustain the effect from chemotherapeutic induction.