可切除非小细胞肺癌的新辅助靶向治疗：目前和未来展望

SCI

15 July 2023

Neoadjuvant Targeted Therapy in Resectable Non-Small Cell Lung Cancer: Current and Future Perspectives 

（Journal of Thoracic Oncology, IF: 20.4）

Lee JM, McNamee CJ, Toloza E, Negrao MV, Lin J, Shum E, Cummings AL, Kris MG, Sepesi B, Bara I, Kurtsikidze N, Schulze K, Ngiam C, Chaft JE 

CORRESPONDENCE TO: jaymoonlee@mednet.ucla.edu

The standard of care (SoC) for medically operable patients with early-stage (stage I–IIIB) non-small cell lung cancer (NSCLC) is surgery combined with (neo)adjuvant systemic therapy for patients with II–IIIB disease and some stage IB or, rarely, chemoradiation (stage III disease with mediastinal lymph node metastases). Despite these treatments, metastatic recurrence is common and associated with poor survival, highlighting the need for systemic therapies that are more effective than the current SoC. Following the success of targeted therapy (TT) in patients with advanced NSCLC (aNSCLC) harboring oncogenic drivers, these agents are being investigated for the perioperative (neoadjuvant and adjuvant) treatment of patients with early-stage NSCLC (eNSCLC). Adjuvant osimertinib is the only TT approved for use in the early-stage setting and there are no approved neoadjuvant TTs. We discuss the importance of comprehensive biomarker testing at diagnosis to identify individuals who may benefit from neoadjuvant targeted treatments and review emerging data from neoadjuvant TT trials. We also address the potential challenges for establishing neoadjuvant TTs as SoC in the early-stage setting, including the identification and validation of early response markers to guide care and accelerate drug development, and discuss safety considerations in the perioperative setting. Initial data indicate that neoadjuvant TTs are effective and well tolerated in patients with EGFR- or ALK-positive eNSCLC. Data from ongoing trials will determine whether neoadjuvant targeted agents will become a new SoC for individuals with oncogene-addicted resectable NSCLC.

早期（I–IIIB期）非小细胞肺癌的可手术患者的标准治疗（SoC）是手术结合（新）辅助全身治疗，适用于II–IIIB期和某些IB期患者，或少数化疗（III期疾病伴纵隔淋巴结转移）。尽管有这些治疗，但转移性复发常见，并与低生存率相关，因此提出了比目前SoC更有效的系统治疗的需求。随着靶向治疗成功治疗携带致癌驱动因素的晚期非小细胞肺癌患者后，正在研究这些药物用于早期非小细胞癌患者的围手术期（新辅助和辅助）治疗。Osimertinib作为唯一获批用于早期肿瘤的辅助靶向治疗，目前尚无获批的新辅助靶向治疗。本文讨论了生物标志物综合检测在诊断中的重要性，以确定可能受益于新辅助靶向治疗的个体，并回顾了新辅助靶向治疗的新试验数据。我们还解决了早期肿瘤中确立新辅助靶向治疗为SoC的潜在挑战，包括早期反应标志物的识别和验证，以指导治疗和加速药物开发，并讨论了围手术期的安全性问题。初步数据表明，新辅助靶向治疗对EGFR或ALK阳性早期非小细胞癌患者有效且耐受性良好。正在进行的试验数据将确定新靶向药物是否会成为致癌基因依赖、可切除NSCLC患者的新SoC。