美国安德森癌症医学中心John V. Heymach团队研究了德鲁单抗用于可切除非小细胞肺癌患者围手术期治疗的效果。该研究于2023年10月23日发表在《新英格兰医学杂志》上。

新辅助或辅助免疫疗法可以改善可切除的非小细胞肺癌癌症（NSCLC）患者的预后。围手术期治疗方案可将两者的益处结合起来，以改善长期疗效。

根据第八版AJCC癌症分期手册，研究组随机分配可切除NSCLC患者（II期至IIIB期[N2结期]）接受基于铂的化疗加上德鲁单抗或安慰剂，每3周静脉注射一次，为期4个周期，然后每4周静脉注射辅助德鲁单抗和安慰剂，为期12个周期。根据疾病分期（II或III）和程序性死亡配体1（PD-L1）表达（≥1%或<1%）对随机分组进行分层。主要终点是无事件生存期（定义为无法手术或阻止手术完成的进行性疾病、疾病复发[通过独立的中央审查以盲法评估]或全因死亡的最早发生时间）和病理学完全缓解（中央评估）。

共有802名患者被随机分配接受德鲁单抗（400名患者）或安慰剂（402名患者）治疗。德鲁单抗的无事件生存期明显长于安慰剂；在第一次中期分析中，疾病进展、复发或死亡的分层危险比为0.68（P=0.004）。在12个月的里程碑分析中，73.4%接受德鲁单抗治疗的患者观察到无事件生存，接受安慰剂的患者中有64.5%。德鲁单抗的病理学完全缓解发生率显著高于安慰剂（最终分析为17.2%对4.3%；差异13.0个百分点；对402名患者的数据进行中期分析时P<0.001）。无论分期和PD-L1表达如何，均观察到无事件生存和病理学完全缓解的益处。42.4%的德鲁单抗患者和43.2%的安慰剂患者发生了最高级别为3或4级的不良事件。来自62名有EGFR或ALK突变记录患者的数据被排除在改良意向治疗人群的疗效分析之外。

研究结果表明，在可切除的NSCLC患者中，与单独新辅助化疗相比，围手术期德鲁单抗联合新辅助化疗与更高的无事件生存率和病理学完全缓解相关，其安全性与个体药物一致。

附：英文原文

Title: Perioperative Durvalumab for Resectable Non–Small-Cell Lung Cancer | NEJM

Author: anonymous

Issue&Volume: 2023-10-23

Abstract:

Background

Neoadjuvant or adjuvant immunotherapy can improve outcomes in patients with resectable non–small-cell lung cancer (NSCLC). Perioperative regimens may combine benefits of both to improve long-term outcomes.

Methods

We randomly assigned patients with resectable NSCLC (stage II to IIIB [N2 node stage] according to the eighth edition of the AJCC Cancer Staging Manual) to receive platinum-based chemotherapy plus durvalumab or placebo administered intravenously every 3 weeks for 4 cycles before surgery, followed by adjuvant durvalumab or placebo intravenously every 4 weeks for 12 cycles. Randomization was stratified according to disease stage (II or III) and programmed death ligand 1 (PD-L1) expression (≥1% or <1%). Primary end points were event-free survival (defined as the time to the earliest occurrence of progressive disease that precluded surgery or prevented completion of surgery, disease recurrence [assessed in a blinded fashion by independent central review], or death from any cause) and pathological complete response (evaluated centrally).

Results

A total of 802 patients were randomly assigned to receive durvalumab (400 patients) or placebo (402 patients). The duration of event-free survival was significantly longer with durvalumab than with placebo; the stratified hazard ratio for disease progression, recurrence, or death was 0.68 (95% confidence interval [CI], 0.53 to 0.88; P=0.004) at the first interim analysis. At the 12-month landmark analysis, event-free survival was observed in 73.4% of the patients who received durvalumab (95% CI, 67.9 to 78.1), as compared with 64.5% of the patients who received placebo (95% CI, 58.8 to 69.6). The incidence of pathological complete response was significantly greater with durvalumab than with placebo (17.2% vs. 4.3% at the final analysis; difference, 13.0 percentage points; 95% CI, 8.7 to 17.6; P<0.001 at interim analysis of data from 402 patients). Event-free survival and pathological complete response benefit were observed regardless of stage and PD-L1 expression. Adverse events of maximum grade 3 or 4 occurred in 42.4% of patients with durvalumab and in 43.2% with placebo. Data from 62 patients with documented EGFR or ALK alterations were excluded from the efficacy analyses in the modified intention-to-treat population.

Conclusions

In patients with resectable NSCLC, perioperative durvalumab plus neoadjuvant chemotherapy was associated with significantly greater event-free survival and pathological complete response than neoadjuvant chemotherapy alone, with a safety profile that was consistent with the individual agents.

DOI: 10.1056/NEJMoa2304875

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2304875