不可切除的 III 期非小细胞肺癌序贯放化疗后使用度伐鲁单抗——II 期 PACIFIC-6 试验的最终分析
Durvalumab after sequential chemoradiotherapy in unresectable stage III non-small-cell lung cancer-final analysis from the phase II PACIFIC-6 trial.
作者信息
Garassino M C, Khalifa J, Reck M, Chouaid C, Bischoff H, Reinmuth N, Cove-Smith L, Mansy T, Cortinovis D L, Migliorino M R, Delmonte A, Garcia Sánchez J, Chara Velarde L E, Bernabe R, Paz-Ares L, Chander P, Diaz Perez I, Foroutanpour K, Emeribe U, Faivre-Finn C
机构信息
Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Hematology/Oncology, The University of Chicago, Chicago, USA.
Oncopole Claudius Regaud, Toulouse, France.
出版信息
ESMO Open. 2025 Jun;10(6):105071. doi: 10.1016/j.esmoop.2025.105071. Epub 2025 May 27.
BACKGROUND
Durvalumab after concurrent chemoradiotherapy (cCRT) is the standard of care for patients with unresectable, stage III non-small-cell lung cancer (NSCLC). However, patients often receive sequential chemoradiotherapy (sCRT) due to factors including advanced age or frailty, comorbidities, or disease- or access-related concerns. The phase II PACIFIC-6 trial (NCT03693300) evaluated the safety of durvalumab after sCRT in this setting. Interim results indicated a similar safety profile to that observed with durvalumab after cCRT, with encouraging preliminary efficacy. We report outcomes from the final analysis.
PATIENTS AND METHODS
Adults with unresectable, stage III NSCLC, Eastern Cooperative Oncology Group performance status ≤2, and no disease progression following platinum-based sCRT were enrolled to receive durvalumab 1500 mg intravenously once every 4 weeks for up to 24 months. The primary endpoint was the incidence of grade 3/4 adverse events (AEs) possibly related to treatment (PRAEs) occurring within 6 months. Secondary endpoints included overall survival (OS) and progression-free survival (PFS; investigator assessed as per RECIST v1.1).
RESULTS
As of 20 March 2023, 117 patients (65.8% aged ≥65 years; 98.3% with past or present comorbidities) were enrolled. Overall, 27.4% of patients had grade 3/4 AEs and 6.0% had grade 3/4 PRAEs, including two patients (1.7%) with pneumonitis. Three patients (2.6%) had fatal AEs, with one (0.9%) having a fatal PRAE (pneumonitis). Overall, 27.4% discontinued durvalumab due to AEs. Median follow-up was 32.6 and 30.2 months among patients censored for OS and PFS, respectively. Median OS was 39.0 months [95% confidence interval (CI) 30.6 months-not calculable]; 3-year OS rate was 56.5% (95% CI 46.4% to 65.5%). Median PFS was 13.1 months (95% CI 7.4-19.9 months); 2-year PFS rate was 35.3% (95% CI 26.5% to 44.3%).
CONCLUSIONS
Durvalumab after sCRT was well tolerated and could be an alternative treatment strategy when cCRT is not feasible. Confirmatory randomized phase III data are awaited.
背景
同步放化疗（cCRT）后使用度伐利尤单抗是不可切除的 III 期非小细胞肺癌（NSCLC）患者的标准治疗方案。然而，由于高龄或身体虚弱、合并症、疾病或治疗可及性相关问题等因素，患者常接受序贯放化疗（sCRT）。II 期 PACIFIC-6 试验（NCT03693300）评估了在这种情况下 sCRT 后使用度伐利尤单抗的安全性。中期结果表明，其安全性与 cCRT 后使用度伐利尤单抗时观察到的相似，初步疗效令人鼓舞。我们报告最终分析的结果。
患者与方法
纳入不可切除的 III 期 NSCLC 成年患者，东部肿瘤协作组体能状态≤2，且在铂类 sCRT 后无疾病进展，接受度伐利尤单抗 1500 mg 静脉注射，每 4 周 1 次，最长 24 个月。主要终点是 6 个月内发生的可能与治疗相关的 3/4 级不良事件（AE）的发生率。次要终点包括总生存期（OS）和无进展生存期（PFS；研究者根据 RECIST v1.1 进行评估）。
结果
截至 2023 年 3 月 20 日，共纳入 117 例患者（65.8%年龄≥65 岁；98.3%有既往或当前合并症）。总体而言，27.4%的患者发生 3/4 级 AE，6.0%的患者发生 3/4 级可能与治疗相关的 AE（PRAE），包括 2 例（1.7%）肺炎患者。3 例患者（2.6%）发生致命 AE，其中 1 例（0.9%）发生致命 PRAE（肺炎）。总体而言，27.4%的患者因 AE 停用度伐利尤单抗。分别对 OS 和 PFS 进行 censored 的患者，中位随访时间分别为 32.6 个月和 30.2 个月。中位 OS 为 39.0 个月[95%置信区间（CI）30.6 个月 - 不可计算]；3 年 OS 率为 56.5%（95%CI 46.4%至 65.5%）。中位 PFS 为 13.1 个月（95%CI 7.4 - 19.9 个月）；2 年 PFS 率为 35.3%（95%CI 26.5%至 44.3%）。
结论
sCRT 后使用度伐利尤单抗耐受性良好，当 cCRT 不可行时可能是一种替代治疗策略。有待确证性随机 III 期数据。
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