Since 2012 when immune checkpoint inhibitors reported the first signals of activity in advanced non-small cell lung cancer (NSCLC), 1,2 immunotherapy has progressively revolutionized the therapeutic landscape of this disease moving from pretreated metastatic disease to earlier stages, including the resectable setting. 3 Platinum-based chemotherapy has been the mainstay of treatment for early-stage NSCLC over the last few decades with a modest but clinically significant survival advantage of approximately 5% at 5 years either as adjuvant 4 or neoadjuvant therapy. 5 However, long-term outcomes of resected NSCLC are still modest, and a significant percentage of patients' disease still recurs after a curative intent treatment. The feasibility and safety of neoadjuvant immunotherapy was first evaluated in a small seminal pilot study 6 with nivolumab monotherapy in 2018. Neoadjuvant single agent programmable cell death-1 (PD-1) blockage with nivolumab at a dose of 3 mg/kg every 2 weeks and surgery planned approximately 4 weeks after the first dose was feasible with few adverse events and no surgery delay, and induced a major pathological response (MPR) in 45% of resected stage I-IIIA tumors, with responses occurring in both programmed cell death ligand 1 (PD-L1)-positive and PD-L1negative tumors. This prompted the design of several phase II/III trials evaluating different immunotherapy-based regimens including single-agent PD-1/PD-L1 inhibitors, dual-checkpoint blockage with PD-1/CTLA-4 inhibitors and chemoimmunotherapy combinations. Among these strategies, chemoimmunotherapy has emerged as the most promising in terms of efficacy and tolerability, as chemotherapy-free regimens are collectively associated with lower overall response rates and MPR rates. 7 In JAMA Oncology, Sorin et al 8 reported the results of a metaanalysis comparing chemoimmunotherapy with chemotherapy alone in resectable NSCLC. Data of 4045 patients from 39 eligible studies, including 5 randomized clinical trials, were analyzed, showing that neoadjuvant chemoimmunotherapy was superior to chemotherapy alone in terms of overall survival (OS) (hazard ratio [HR], 0.65), event-free survival (EFS) (HR, 0.59), MPR (risk ratio [RR], 3.42), and complete pathological response (pCR) (RR, 5.52). 8 EFS benefit was observed regardless of disease age (HR, 0.54 in patients <65 years and HR, 0.66 in patients ≥65 years), sex, histology (squamous vs nonsquamous), and PD-L1 expression, including PD-L1-negative tumors (HR, 0.74; 95% CI, 0.62-0.89; I 2 = 0%), albeit the magnitude of benefit was higher in PD-L1 of 1% to 49% (HR, 0.56; 95% CI, 0.42-0.73; I 2 = 41.3%) and PD-L1 strong expressors (HR, 0.40; 95% CI, 0.28-0.56; I 2 = 32.1%).The role of neoadjuvant chemoimmunotherapy in PD-L1negative tumors is one of the most significant data emerging from the present meta-analysis. 8 This is particularly relevant,
