Five-Year Outcomes From the Randomized, Phase III Trials CheckMate 017 and 057: Nivolumab Versus Docetaxel in Previously Treated Non-Small-Cell Lung Cancer.
Five-Year Outcomes From the Randomized, Phase III Trials CheckMate 017 and 057: Nivolumab Versus Docetaxel in Previously Treated Non-Small-Cell Lung Cancer.
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DOI：
10.1200/jco.20.01605
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发表时间：
2021-03-01
期刊：
影响因子：
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通讯作者：
Brahmer J
中科院分区：
文献类型：
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作者：
Borghaei H;Gettinger S;Vokes EE;Chow LQM;Burgio MA;de Castro Carpeno J;Pluzanski A;Arrieta O;Frontera OA;Chiari R;Butts C;Wójcik-Tomaszewska J;Coudert B;Garassino MC;Ready N;Felip E;García MA;Waterhouse D;Domine M;Barlesi F;Antonia S;Wohlleber M;Gerber DE;Czyzewicz G;Spigel DR;Crino L;Eberhardt WEE;Li A;Marimuthu S;Brahmer J
免疫疗法已经彻底改变了晚期非小细胞肺癌（NSCLC）的治疗。在两项III期试验（CheckMate 017和CheckMate 057）中，与多西他赛相比，nivolumab分别在先前治疗过的晚期鳞状和非鳞状NSCLC患者中显示出总体生存期（OS）的改善和良好的安全性。我们报告了这些试验的5年疗效和安全性汇总。在一线铂基化疗期间或之后，ECOG PS≤1且进展的晚期NSCLC患者（N = 854； CheckMate 017/057合并）被随机按1:1分配到纳沃单抗（3mg /kg每2周1次）或多西他赛（75mg /m2每3周1次），直到进展或不可接受的毒性。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。探索性地标分析进行了调查。在CheckMate 017和057的最短随访时间分别为64.2和64.5个月后，50名纳武单抗治疗的患者和9名多西他赛治疗的患者存活。5年合并OS率分别为13.4%和2.6%；5年PFS分别为8.0%和0%。nivolumab治疗的患者在2年和3年无疾病进展的生存率分别为82.0%和93.0%，5年无疾病进展的生存率分别为59.6%和78.3%。在3-5年随访期间，31名接受尼伏单抗治疗的患者中有8名（25.8%）报告了治疗相关不良事件（TRAEs），其中7名出现了新事件；1例（3.2%）TRAE为3级，无4级TRAE。在5年时，nivolumab继续显示出与多西他赛相比的生存获益，显示出OS率增加了5倍，没有新的安全性信号。这些数据代表了一种程序性死亡-1抑制剂在先前治疗的晚期NSCLC中随机III期试验的5年结果的第一份报告。
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. 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/m2 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. 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. 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.