Schuler Martin
Department of Medical Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany.
Medical Faculty, University Duisburg-Essen, Essen, Germany.
Clin Cancer Res. 2025 Mar 3;31(5):801-807. doi: 10.1158/1078-0432.CCR-24-1441.
Antibodies targeting immune checkpoints, such as PD-1, PD-L1, or CTLA-4, have transformed the treatment of patients with lung cancers. Unprecedented rates of durable responses are achieved in an imperfectly characterized population of patients with metastatic disease. More recently, immune checkpoint inhibitors have been explored in patients with resectable non-small cell lung cancers. Following a traditional paradigm, antibody therapies were first studied in the adjuvant setting, after surgery and chemotherapy. Pivotal trials supported global approvals of the PD-L1/-1 antibodies atezolizumab and pembrolizumab in this setting. Exciting observations were made when checkpoint inhibitors were moved to the preoperative window. Several signal-finding studies explored a limited number of cycles prior to surgery and reproducibly reported complete or major histopathologic responses. So far, six published phase III trials have demonstrated the superiority of combining the PD-1/-L1 antibodies nivolumab, pembrolizumab, durvalumab, tislelizumab, or toripalimab with 3 to 4 courses of preoperative platinum-based chemotherapy over preoperative chemotherapy alone in terms of response rates and survival endpoints. Those patients achieving complete or major histopathologic responses experienced particularly favorable long-term outcomes. It is yet unclear whether there is true synergism between immunotherapy and chemotherapy and whether outcomes are further improved by adding postoperative checkpoint inhibition. Although these pivotal trials qualify neoadjuvant chemoimmunotherapy as another option in curative lung cancer treatment, there is hope that the chemotherapy backbone will be ultimately replaced by rationally selected and targeted combination partners. In this work, the current status and future avenues of neoadjuvant combination immunotherapies in patients with non-small cell lung cancer are reviewed.
靶向免疫检查点（如PD-1、PD-L1或CTLA-4）的抗体已经改变了肺癌患者的治疗方式。在特征尚不明确的转移性疾病患者群体中，实现了前所未有的持久缓解率。最近，免疫检查点抑制剂已在可切除的非小细胞肺癌患者中进行了探索。按照传统模式，抗体疗法首先在辅助治疗中进行研究，即在手术和化疗之后。关键试验支持了PD-L1/-1抗体阿替利珠单抗和帕博利珠单抗在这一情况下获得全球批准。当检查点抑制剂应用于术前阶段时，出现了令人兴奋的观察结果。几项探索性研究在手术前进行了有限疗程的治疗，并反复报告了完全或主要组织病理学缓解情况。到目前为止，六项已发表的III期试验已经证明，在缓解率和生存终点方面，将PD-1/-L1抗体纳武利尤单抗、帕博利珠单抗、度伐利尤单抗、替雷利珠单抗或托瑞帕利单抗与3至4个疗程的术前铂类化疗联合使用，优于单纯术前化疗。那些实现完全或主要组织病理学缓解的患者经历了特别良好的长期预后。目前尚不清楚免疫疗法和化疗之间是否存在真正的协同作用，以及术后添加检查点抑制剂是否能进一步改善预后。尽管这些关键试验使新辅助化疗免疫疗法成为治愈性肺癌治疗的另一种选择，但人们希望化疗的基础最终将被合理选择的靶向联合治疗伙伴所取代。在这项工作中，我们综述了非小细胞肺癌患者新辅助联合免疫疗法的现状和未来发展方向。
