CheckMate 017 和 057 随机、III 期临床试验的 5 年结果：纳武利尤单抗对比多西他赛用于先前治疗的非小细胞肺癌。

PURPOSE: Immunotherapy has revolutionized the treatment of advanced non-small-cell lung cancer (NSCLC). In two phase III trials (CheckMate 017 and CheckMate 057), nivolumab showed an improvement in overall survival (OS) and favorable safety versus docetaxel in patients with previously treated, advanced squamous and nonsquamous NSCLC, respectively. We report 5-year pooled efficacy and safety from these trials. METHODS: Patients (N = 854; CheckMate 017/057 pooled) with advanced NSCLC, ECOG PS ≤ 1, and progression during or after first-line platinum-based chemotherapy were randomly assigned 1:1 to nivolumab (3 mg/kg once every 2 weeks) or docetaxel (75 mg/m once every 3 weeks) until progression or unacceptable toxicity. The primary end point for both trials was OS; secondary end points included progression-free survival (PFS) and safety. Exploratory landmark analyses were investigated. RESULTS: After the minimum follow-up of 64.2 and 64.5 months for CheckMate 017 and 057, respectively, 50 nivolumab-treated patients and nine docetaxel-treated patients were alive. Five-year pooled OS rates were 13.4% versus 2.6%, respectively; 5-year PFS rates were 8.0% versus 0%, respectively. Nivolumab-treated patients without disease progression at 2 and 3 years had an 82.0% and 93.0% chance of survival, respectively, and a 59.6% and 78.3% chance of remaining progression-free at 5 years, respectively. Treatment-related adverse events (TRAEs) were reported in 8 of 31 (25.8%) nivolumab-treated patients between 3-5 years of follow-up, seven of whom experienced new events; one (3.2%) TRAE was grade 3, and there were no grade 4 TRAEs. CONCLUSION: At 5 years, nivolumab continued to demonstrate a survival benefit versus docetaxel, exhibiting a five-fold increase in OS rate, with no new safety signals. These data represent the first report of 5-year outcomes from randomized phase III trials of a programmed death-1 inhibitor in previously treated, advanced NSCLC.

目的：免疫疗法彻底改变了晚期非小细胞肺癌（NSCLC）的治疗方式。在两项 III 期临床试验（CheckMate 017 和 CheckMate 057）中，纳武利尤单抗与多西他赛相比，分别在先前接受过治疗的晚期鳞状和非鳞状 NSCLC 患者中，提高了总生存期（OS）并具有更好的安全性。我们报告了这些试验的 5 年汇总疗效和安全性数据。

方法：患有晚期 NSCLC、ECOG PS ≤ 1 且在一线含铂化疗期间或之后发生进展的患者（CheckMate 017/057 汇总），按 1:1 随机分配至纳武利尤单抗（3 mg/kg，每 2 周一次）或多西他赛（75 mg/m2，每 3 周一次）治疗，直至疾病进展或出现不可接受的毒性。两项试验的主要终点均为 OS；次要终点包括无进展生存期（PFS）和安全性。进行了探索性里程碑分析。

结果：在 CheckMate 017 和 057 分别进行了至少 64.2 和 64.5 个月的随访后，分别有 50 名纳武利尤单抗治疗患者和 9 名多西他赛治疗患者存活。5 年总生存率分别为 13.4%和 2.6%；5 年 PFS 率分别为 8.0%和 0%。在 2 年和 3 年无疾病进展的纳武利尤单抗治疗患者，分别有 82.0%和 93.0%的生存机会，分别有 59.6%和 78.3%的无进展生存机会，分别在 5 年时仍保持无进展。在随访 3-5 年期间，8 名（25.8%）纳武利尤单抗治疗患者报告了 3-5 级治疗相关不良事件（TRAEs），其中 7 名患者出现新的事件；1 名（3.2%）TRAEs 为 3 级，无 4 级 TRAEs。

结论：5 年时，纳武利尤单抗与多西他赛相比继续显示出生存获益，OS 率提高了 5 倍，没有新的安全性信号。这些数据代表了程序性死亡-1 抑制剂在先前治疗的晚期 NSCLC 的随机 III 期试验中首次报告 5 年结果。