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 adjuvant⁴ 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 study⁶ 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-L1–negative 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