The Chemoimmunotherapy Revolution in Resectable NSCLC—The Times They Are A-Changin’
A partir d'une revue systématique de la littérature (43 essais, 5 431 patients), cette méta-analyse évalue l'efficacité des chimio-immunothérapies néoadjuvantes pour traiter un cancer du poumon non à petites cellules
Since 2012 when immune checkpoint inhibitors reported the first signals of activity in advanced non–small cell lung cancer (NSCLC), immunotherapy has progressively revolutionized the therapeutic landscape of this disease moving from pretreated metastatic disease to earlier stages, including the resectable setting. 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 or neoadjuvant therapy. 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 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.