Perioperative Therapy for Non-Small Cell Lung Cancer with Immune Checkpoint Inhibitors

SIMPLE SUMMARY: This review presents the development of perioperative treatment using immune checkpoint inhibitors (ICIs) in patients with resectable non-small cell lung cancers. There are several ongoing phase 3 trials for adjuvant and neoadjuvant ICI therapies. The results of the adjuvant (IMpower010 trial) and the neoadjuvant (Checkmate 816 trial) ICI phase 3 trials have shown prolonged disease-free survival and increased pathological complete response rate, respectively. Based on the hypothesis that ‘preoperative ICI treatment, especially in combination with conventional chemotherapy, promotes a higher immune response because of preservation of the immune environment’, neoadjuvant trials using ICIs and conventional chemotherapy in combination are currently being conducted more frequently than adjuvant ICI trials. Multimodality approaches using chemoradiotherapy and new ICI agents are also being examined in several phase 2 trials. To maximise ICI therapy’s efficacy and to minimise futile administration, methodologies for predicting and monitoring the therapeutic effects, such as detecting minimal residual disease, need to be established. ABSTRACT: The emergence of immune checkpoint inhibitors (ICIs) has dramatically changed the treatment landscape for patients with metastatic non-small cell lung cancer (NSCLC). These achievements inspired investigators and pharmaceutical companies to conduct clinical trials in patients with early-stage NSCLC because both adjuvant and neoadjuvant platinum-based doublet chemotherapies (PT-DCs) showed only a 5% improvement in 5-year overall survival. IMpower010, a phase 3 trial (P3), showed that adjuvant PT-DC followed by maintenance atezolitumab significantly prolonged disease-free survival over adjuvant PT-DC alone (hazard ratio, 0.79; stage II to IIIA). Since conventional therapies, including chemotherapy and radiotherapy, can promote immunogenic cell death, releasing tumour antigens from dead tumour cells, ICI combination therapies with conventional therapies are widely proposed. The Checkmate 816 trial (P3) indicated a significantly higher pathological complete response rate of neoadjuvant nivolumab/PT-DC combination therapy than of neoadjuvant PT-DC alone (odds ratio, 13.9, for stage IB to IIIA). Detection of circulating tumour DNA is highly anticipated for the evaluation of minimal residual disease. Multimodal approaches and new ICI agents are being attempted to improve the efficacy of ICI treatment in phase 2 trials. This review presents the development of perioperative treatment using ICIs in patients with NSCLC while discussing problems and perspectives.