Safety and Efficacy of Neoadjuvant Immune Checkpoint Inhibitor Therapy in Patients with Resectable Non-small-Cell Lung Cancer: A Systematic Review

Background Non-small-cell lung cancer (NSCLC) accounts for most new diagnoses of lung cancer, with high morbidity and mortality worldwide. Immune checkpoint inhibitor (ICI) therapy has transformed the treatment of metastatic and advanced NSCLC. For resectable NSCLC, while surgery is the cornerstone of standard treatment, a number of clinical trials of neoadjuvant immunotherapy have been conducted. Objective To perform a systematic review on the safety and efficacy of neoadjuvant ICI therapy in patients with resectable NSCLC. Methods This systematic review was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. We undertook a comprehensive literature search of PubMed, Embase, Cochrane Library, and abstracts and posters from annual meetings of the major oncology societies, American Society of Clinical Oncology (ASCO), European Society for Medical Oncology (ESMO), American Association for Cancer Research (AACR) up until 29 April 2021. Results A total of 399 patients were identified from six articles and four meeting abstracts. 229, 140, and 30 patients received anti-programmed cell death ligand 1 therapy (anti-PD-L1, atezolizumab and durvalumab), anti-programmed cell death 1 therapy (anti-PD-1, nivolumab, pembrolizumab, sintilimab), and anti-PD-1/anti-CTLA-4 combination therapy (nivolumab and ipilimumab), respectively. 255 patients received only ICI therapy before surgery, and 144 patients received ICI and chemotherapy. While ICI therapy was generally well tolerated, grade 3 or higher immune-related adverse events were observed in 13 of 144 patients (9.0%) in the five studies that reported such adverse events data. Patients displayed an overall mean surgical resection rate of 87.5% (349/399, range, 66.7–100%), a surgical delay rate of 1.4%, and an incidence of surgical complications of 21%. On average, 45.6% (159/349), (range 17–83%) of patients exhibited major pathological response (MPR), while 76/349 (21.8%) patients achieved pathological complete response (pCR). In the studies with patients undergoing ICI and chemotherapy, the MPR rate was 66.7% and pCR rate was 35.4%. Conclusions ICI neoadjuvant therapy may be a safe and efficacious treatment option in patients with resectable NSCLC. Combined with chemotherapy, ICI appears to be more efficacious, but displays more adverse events. More ongoing clinical trials will shed further light on the safety and efficacy of ICI neoadjuvant therapy in patie