The University of Manchester, Manchester, United Kingdom; The Christie NHS Foundation Trust, Manchester, United Kingdom.
Department of Medical Oncology, Hospital Universitario Virgen Macarena, Seville, Spain.
J Thorac Oncol. 2021 May;16(5):860-867. doi: 10.1016/j.jtho.2020.12.015. Epub 2021 Jan 19.
In the Phase 3, placebo-controlled PACIFIC trial of patients with unresectable, stage III NSCLC without disease progression after concurrent chemoradiotherapy, consolidative durvalumab was associated with significant improvements in the primary end points of overall survival (OS) (hazard ratio [HR] = 0.68; 95% confidence interval [CI]: 0.53-0.87; p = 0.00251; data cutoff, March 22, 2018) and progression-free survival (PFS) (blinded independent central review; Response Evaluation Criteria in Solid Tumors version 1.1) (HR = 0.52; 95% CI: 0.42-65; p < 0.0001; February 13, 2017) with manageable safety. Here, we report updated analyses of OS and PFS, approximately 4 years after the last patient was randomized.
Patients with WHO performance status of 0 or 1 (and any tumor programmed death-ligand 1 status) were randomized (2:1) to intravenous durvalumab (10 mg/kg) or placebo, administered every 2 weeks (≤12 months), stratified by age, sex, and smoking history. OS and PFS were analyzed using a stratified log-rank test in the intent-to-treat population. Medians and 4-year OS and PFS rates were estimated by the Kaplan-Meier method.
Overall, 709 of 713 randomized patients received durvalumab (n/N=473/476) or placebo (n/N=236/237). As of March 20, 2020 (median follow-up = 34.2 months; range: 0.2-64.9), updated OS (HR = 0.71; 95% CI: 0.57-0.88) and PFS (HR = 0.55; 95% CI: 0.44-0.67) remained consistent with the primary analyses. The median OS for durvalumab was reached (47.5 mo; placebo, 29.1 months). Estimated 4-year OS rates were 49.6% versus 36.3% for durvalumab versus placebo, and 4-year PFS rates were 35.3% versus 19.5% respectively.
These updated exploratory analyses demonstrate durable PFS and sustained OS benefit with durvalumab after chemoradiotherapy. An estimated 49.6% of patients randomized to durvalumab remain alive at 4 years (placebo, 36.3%), and 35.3% remain alive and progression-free (placebo, 19.5%).
在 III 期、安慰剂对照 PACIFIC 试验中，对未接受根治性治疗、同步放化疗后无疾病进展的不可切除 III 期非小细胞肺癌患者进行巩固性 durvalumab 治疗，与总生存期（OS）（风险比 [HR]0.68；95%置信区间 [CI]0.53-0.87；p=0.00251；数据截止日期，2018 年 3 月 22 日）和无进展生存期（PFS）（盲法独立中央审查；实体瘤反应评价标准 1.1 版）（HR0.52；95%CI0.42-65；p<0.0001；2017 年 2 月 13 日）的主要终点显著改善相关，安全性可控。在此，我们报告了大约在最后一名患者随机分组后 4 年时对 OS 和 PFS 的更新分析。
WHO 体能状态为 0 或 1（且任何肿瘤程序性死亡配体 1 状态）的患者随机（2:1）接受静脉 durvalumab（10mg/kg）或安慰剂，每 2 周（≤12 个月）给药，分层因素为年龄、性别和吸烟史。在意向治疗人群中，使用分层对数秩检验对 OS 和 PFS 进行分析。通过 Kaplan-Meier 法估计中位数和 4 年 OS 和 PFS 率。
总体而言，713 名随机患者中，709 名（n/N=473/476）接受 durvalumab，236 名（n/N=236/237）接受安慰剂。截至 2020 年 3 月 20 日（中位随访 34.2 个月；范围：0.2-64.9），更新后的 OS（HR0.71；95%CI0.57-0.88）和 PFS（HR0.55；95%CI0.44-0.67）与主要分析结果一致。durvalumab 的中位 OS 达到（47.5mo；安慰剂为 29.1 个月）。估计 4 年 OS 率分别为 durvalumab 组为 49.6%，安慰剂组为 36.3%，4 年 PFS 率分别为 durvalumab 组为 35.3%，安慰剂组为 19.5%。
这些更新的探索性分析表明，在放化疗后，durvalumab 具有持久的 PFS 和持续的 OS 获益。估计有 49.6%随机接受 durvalumab 治疗的患者在 4 年时存活（安慰剂组为 36.3%），35.3%的患者存活且无疾病进展（安慰剂组为 19.5%）。
