Neoadjuvant immunotherapy in early stage non-small cell lung cancer

Abstract

Cancer immunotherapies targeting CTLA-4 and PD-1/PD-L1 relieve tumour induced immune suppression and induce durable tumour regression. When used alone or in combination with other modalities, immune checkpoint inhibitors have had a remarkable clinical impact on the treatment of multiple tumour sites including non-small cell lung cancer (NSCLC). This makes neoadjuvant immunotherapy an attractive option for use in early stage NSCLC. Currently, immunotherapy is used in the UK in both a curative and palliative setting. The use of neoadjuvant immunotherapy has the potential benefit of pathological downstaging prior to surgery, which may facilitate radical approaches to surgery— potentially conferring an improvement in overall survival. This literature review examines current literature and evidence on the use of immunotherapy prior to surgery, both as a single agent and in combination with chemotherapy. We conclude that neoadjuvant immunotherapy is a safe and feasible option for patients with resectable early stage NSCLC. Further investigation is required to determine whether a combined approach with chemotherapy or single agent immunotherapy is superior. Confirmatory Phase III clinical trials are ongoing to assess longer clinical impact on event-free survival (EFS), disease-free survival (DFS) and OS. Predictive and prognostic biomarkers are also needed in this setting, and ongoing work is being conducted to investigate this further.