Paris-Saclay University and Department of Medical Oncology, Gustave Roussy, Villejuif, France; Department of Medical and Surgical Sciences and Translational Medicine, St Andrea University Hospital, Sapienza University, Rome, Italy.
Paris-Saclay University and Department of Medical Oncology, Gustave Roussy, Villejuif, France.
Cancer Treat Rev. 2024 Dec;131:102845. doi: 10.1016/j.ctrv.2024.102845. Epub 2024 Oct 16.
About one third of patients with Non-Small Cell Lung Cancer (NSCLC) presents at diagnosis with localized or locally advanced disease amenable to curative surgical resection. Surgical operability refers to stage I to IIIA and selected stage IIIB NSCLC. One of the main challenges in the management of early-stage resectable NSCLC is the optimization of available therapeutic strategies to prevent local and distant disease relapse, thus improving survival outcomes. There is evidence supporting the clinical use of both adjuvant and neoadjuvant immunotherapy-based strategies for resected/resectable, stage IB-IIIA NSCLC. Available data from randomized phase III trials have led to the incorporation of several immune checkpoint blockers (ICBs) into the international guidelines for early-stage NSCLC. Preclinical rationale of targeting specific subsets of T-cells by acting early on immune checkpoint receptors (e.g., PD-(L)1 and CTLA-4) is strong. Recent evidence is in favor of the neoadjuvant approach alone or as a part of perioperative strategy, demonstrating survival benefit. Combining neoadjuvant chemotherapy and immunotherapy before surgery results in both pathologic complete response (pCR) and major pathologic response (MPR) improvement, and survival outcomes, with no major safety issues. In this review, we summarize the rationale behind neoadjuvant/perioperative immunotherapy strategies and, due to the clinical relevance of immunotherapy in resectable NSCLC, we provide current evidence of this cutting-edge approach among special populations including older adults, women, and oncogene addicted NSCLC. To conclude, we present future perspectives in the use of immunotherapy for operable NSCLC with a special focus on novel investigational combinations underway.
约三分之一的非小细胞肺癌（NSCLC）患者在诊断时表现为局部或局部晚期疾病，适合根治性手术切除。手术可操作性是指 I 期至 IIIA 期和选择性 IIIB 期 NSCLC。早期可切除 NSCLC 管理的主要挑战之一是优化现有治疗策略以预防局部和远处疾病复发，从而提高生存结果。有证据支持在切除/可切除的 IB-IIIA 期 NSCLC 中使用辅助和新辅助免疫治疗策略。来自随机 III 期试验的现有数据导致将几种免疫检查点抑制剂（ICB）纳入早期 NSCLC 的国际指南。通过早期靶向免疫检查点受体（例如 PD-（L）1 和 CTLA-4）靶向特定 T 细胞亚群的临床前原理是合理的。最近的证据支持单独使用新辅助治疗或作为围手术期策略的一部分，显示出生存获益。在手术前联合新辅助化疗和免疫治疗可提高病理完全缓解（pCR）和主要病理缓解（MPR）率，并改善生存结果，且无重大安全问题。在这篇综述中，我们总结了新辅助/围手术期免疫治疗策略的基本原理，并且由于免疫疗法在可切除 NSCLC 中的临床相关性，我们提供了针对特殊人群（包括老年人、女性和致癌基因依赖型 NSCLC）的这种前沿方法的最新证据。最后，我们重点介绍了在可切除 NSCLC 中使用免疫疗法的未来展望，特别关注正在进行的新的研究性联合治疗。
