Five-Year Survival Outcomes From the PACIFIC Trial: Durvalumab After Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer.
Five-Year Survival Outcomes From the PACIFIC Trial: Durvalumab After Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer.
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太平洋试验的五年生存结果：在III期非小细胞肺癌中进行化学放录后的杜瓦卢马布。
DOI：
10.1200/jco.21.01308
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发表时间：
2022-04-20
期刊：
影响因子：
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通讯作者：
Antonia SJ
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作者：
Spigel DR;Faivre-Finn C;Gray JE;Vicente D;Planchard D;Paz-Ares L;Vansteenkiste JF;Garassino MC;Hui R;Quantin X;Rimner A;Wu YL;Özgüroğlu M;Lee KH;Kato T;de Wit M;Kurata T;Reck M;Cho BC;Senan S;Naidoo J;Mann H;Newton M;Thiyagarajah P;Antonia SJ
III期PACIFIC试验比较了durvalumab与安慰剂在不可切除的III期非小细胞肺癌患者中的疗效，同时放化疗后无疾病进展。巩固durvalumab与总生存期主要终点的显著改善相关（OS;分层风险比[HR]，0.68; 95% CI，0.53至0.87; P = .00251）和无进展生存期（PFS [盲法独立中心审查; RECIST v1.1];分层HR，0.52; 95% CI，0.42 - 0.65; P < .0001），安全性可控。我们报告最新的，探索性的生存分析，大约5年后，最后一个病人被随机分配。WHO体能状态为0或1（任何肿瘤程序性细胞死亡-配体1状态）的患者随机（2：1）分配至durvalumab（10 mg/kg静脉给药;每2周一次，持续12个月）或安慰剂组，按年龄、性别和吸烟史分层。使用分层对数秩检验进行至事件发生时间终点分析。使用Kaplan-Meier方法估计中位数和界标生存率。713名随机分配的患者中有709名接受了durvalumab（473/476）或安慰剂（236/237）。截至2021年1月11日（中位随访期，34.2个月[所有患者]; 61.6个月[删失患者]），更新OS（分层HR，0.72; 95% CI，0.59 - 0.89;中位数，47.5 vs 29.1个月）和PFS（分层HR，0.55; 95% CI，0.45 - 0.68;中位数，16.9 vs 5.6个月）与主要分析保持一致。Durvalumab和安慰剂的OS估计5年率（95% CI）分别为42.9%（38.2 - 47.4）和33.4%（27.3 - 39.6），PFS估计5年率分别为33.1%（28.0 - 38.2）和19.0%（13.6 - 25.2）。这些更新的分析证明了放化疗后durvalumab的稳健和持续OS和持久PFS获益。估计随机分配至durvalumab组的患者中有42.9%在5年时仍然存活，随机分配至durvalumab组的患者中有33.1%仍然存活且无疾病进展，为该背景下的标准治疗建立了新的基准。
The phase III PACIFIC trial compared durvalumab with placebo in patients with unresectable, stage III non–small-cell lung cancer and no disease progression after concurrent chemoradiotherapy. Consolidation durvalumab was associated with significant improvements in the primary end points of overall survival (OS; stratified hazard ratio [HR], 0.68; 95% CI, 0.53 to 0.87; P = .00251) and progression-free survival (PFS [blinded independent central review; RECIST v1.1]; stratified HR, 0.52; 95% CI, 0.42 to 0.65; P < .0001), with manageable safety. We report updated, exploratory analyses of survival, approximately 5 years after the last patient was randomly assigned. Patients with WHO performance status 0 or 1 (any tumor programmed cell death-ligand 1 status) were randomly assigned (2:1) to durvalumab (10 mg/kg intravenously; administered once every 2 weeks for 12 months) or placebo, stratified by age, sex, and smoking history. Time-to-event end point analyses were performed using stratified log-rank tests. Medians and landmark survival rates were estimated using the Kaplan-Meier method. Seven hundred and nine of 713 randomly assigned patients received durvalumab (473 of 476) or placebo (236 of 237). As of January 11, 2021 (median follow-up, 34.2 months [all patients]; 61.6 months [censored patients]), updated OS (stratified HR, 0.72; 95% CI, 0.59 to 0.89; median, 47.5 v 29.1 months) and PFS (stratified HR, 0.55; 95% CI, 0.45 to 0.68; median, 16.9 v 5.6 months) remained consistent with the primary analyses. Estimated 5-year rates (95% CI) for durvalumab and placebo were 42.9% (38.2 to 47.4) versus 33.4% (27.3 to 39.6) for OS and 33.1% (28.0 to 38.2) versus 19.0% (13.6 to 25.2) for PFS. These updated analyses demonstrate robust and sustained OS and durable PFS benefit with durvalumab after chemoradiotherapy. An estimated 42.9% of patients randomly assigned to durvalumab remain alive at 5 years and 33.1% of patients randomly assigned to durvalumab remain alive and free of disease progression, establishing a new benchmark for standard of care in this setting.