Comparison of perioperative outcomes among non-small cell lung cancer patients with neoadjuvant immune checkpoint inhibitor plus chemotherapy, EGFR-TKI, and chemotherapy alone: a real- world evidence study

Background: The utilization of neoadjuvant immune checkpoint inhibitor (ICI) plus chemotherapy has increased significantly for resectable non-small cell lung cancer (NSCLC). It is still unclear whether such a treatment paradigm affects perioperative outcomes compared with other neoadjuvant treatment. We aimed to evaluate the perioperative outcomes of pulmonary resection after neoadjuvant ICI plus chemotherapy and to compare them with neoadjuvant epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) and neoadjuvant chemotherapy alone for resectable NSCLC.Methods: A retrospective cohort including 194 stage IB-IIIB NSCLC underwent surgical resection after neoadjuvant treatment between 2018 and 2020 were reviewed. Perioperative complications were evaluated using the Common Terminology Criteria for Adverse Events, and were compared using one-way analysis of variance for continuous variables and Pearson chi-square test.Results: There were 42, 54, and 98 patients in the neoadjuvant ICI plus chemotherapy, EGFR-TKI, and chemotherapy alone groups, respectively. The tumor size before neoadjuvant treatment was well balanced among the three groups (P=0.122). A shorter median surgical time was observed in the EGFR-TKI group than ICI plus chemotherapy group and chemotherapy group alone (120 vs. 150 vs. 146 min, P=0.041). Video -assisted thoracoscopic surgery was performed in 37 (88.1%), 49 (90.7%), and 57 (58.7%) patients in the three groups, respectively (P<0.001). A higher incidence of pneumonia (P=0.014) was found in the chemotherapy group. Perioperative mortality was observed in 1 patient (2.4%) in the ICI plus chemotherapy group and in 3 patients (3.1%) in the chemotherapy alone group (P=0.440). Patients in the ICI plus chemotherapy group had higher proportions of pathological complete response (40.5% vs. 11.1% vs. 6.1%, P<0.001) and downstaging of clinical N2 status (68.6% vs. 42.9% vs. 31.7%, P=0.012) than patients in EGFR-TKI group and chemotherapy alone group.Conclusions: Surgical resection for NSCLC following neoadjuvant ICI plus chemotherapy was safe and feasible, the perioperative outcomes were similar with neoadjuvant EGFR-TKI and chemotherapy alone without unexpected perioperative complications. Additional prospective studies are necessary to validate our findings.