Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland.
Duke University School of Medicine, Durham, North Carolina.
J Thorac Oncol. 2023 May;18(5):657-663. doi: 10.1016/j.jtho.2023.02.009. Epub 2023 Feb 24.
INTRODUCTION: Consolidation durvalumab (the "PACIFIC regimen") is standard of care for patients with unresectable stage III NSCLC who have not progressed after chemoradiotherapy, on the basis of data from the phase 3 placebo-controlled PACIFIC study (NCT02125461). Nevertheless, the benefit of immunotherapy in patients with stage III EGFR-mutant (EGFRm) NSCLC is not well characterized. Here, we report a post hoc exploratory efficacy and safety analysis from a subgroup of patients with EGFRm NSCLC from the PACIFIC. METHODS: Patients with stage III unresectable NSCLC and no progression after more than or equal to two cycles of platinum-based concurrent chemoradiotherapy were randomized (2:1) to receive durvalumab (10 mg/kg intravenously every 2 weeks [wk], for up to 1 y) or placebo; stratified by age, sex, and smoking history. Enrollment was not restricted by oncogenic driver gene mutation status or programmed death-ligand 1 expression. Patients with NSCLC with an EGFR mutation, determined by local testing only, were included in this subgroup analysis. The primary end points were progression-free survival (PFS; assessed by blinded independent central review) and overall survival (OS). Secondary end points included objective response rate and safety. Statistical analyses for the subgroup of patients with EGFRm NSCLC were post hoc and considered exploratory. RESULTS: Of 713 patients randomized, 35 had locally confirmed EGFRm NSCLC (durvalumab, n = 24; placebo, n = 11). At data cutoff (January 11, 2021), median duration of follow-up for survival was 42.7 months (range: 3.7-74.3 mo) for all randomized patients in the subgroup. Median PFS was 11.2 months (95% confidence interval [CI]: 7.3-20.7) with durvalumab versus 10.9 months (95% CI: 1.9-not evaluable [NE]) with placebo; hazard ratio = 0.91 (95% CI: 0.39-2.13). Median OS was 46.8 months (95% CI: 29.9-NE) with durvalumab versus 43.0 months (95% CI: 14.9-NE) with placebo; hazard ratio = 1.02 (95% CI: 0.39-2.63). The safety profile of durvalumab was generally consistent with the overall population and known profile for durvalumab. CONCLUSIONS: PFS and OS outcomes with durvalumab were similar to placebo for patients with EGFRm tumors, with wide CIs. These data should be interpreted with caution owing to small patient numbers and lack of a prospective study that evaluates clinical outcomes by tumor biomarker status. Further research to determine the optimal treatment for unresectable stage III EGFRm NSCLC is warranted.
简介:对于未接受放化疗后进展的不可切除 III 期非小细胞肺癌(NSCLC)患者,巩固治疗durvalumab(“PACIFIC 方案”)是标准治疗方法,该方案基于 III 期安慰剂对照 PACIFIC 研究(NCT02125461)的数据。然而,免疫疗法在 III 期表皮生长因子受体突变(EGFRm)NSCLC 患者中的获益尚不清楚。在此,我们报告了 PACIFIC 研究中 EGFRm NSCLC 患者亚组的事后探索性疗效和安全性分析结果。 方法:接受过至少两周期含铂化疗联合放疗后未进展的不可切除 III 期 NSCLC 患者,按 2:1 随机分组,分别接受 durvalumab(10 mg/kg,每 2 周静脉输注 1 次,持续 1 年)或安慰剂;分层因素为年龄、性别和吸烟史。入组不受致癌驱动基因突变状态或程序性死亡配体 1 表达的限制。仅通过局部检测确定存在 EGFR 突变的 NSCLC 患者被纳入本亚组分析。无进展生存期(PFS;由盲法独立中心审查评估)和总生存期(OS)是主要终点。次要终点包括客观缓解率和安全性。EGFRm NSCLC 患者亚组的统计分析是事后分析,被认为是探索性的。 结果:713 例随机患者中,35 例经局部确认存在 EGFRm NSCLC(durvalumab,n=24;安慰剂,n=11)。截至数据截止日期(2021 年 1 月 11 日),所有随机分组患者的中位随访生存时间为 42.7 个月(范围:3.7-74.3 个月)。durvalumab 组的中位 PFS 为 11.2 个月(95%置信区间[CI]:7.3-20.7),安慰剂组为 10.9 个月(95% CI:1.9-NE);风险比为 0.91(95% CI:0.39-2.13)。durvalumab 组的中位 OS 为 46.8 个月(95% CI:29.9-NE),安慰剂组为 43.0 个月(95% CI:14.9-NE);风险比为 1.02(95% CI:0.39-2.63)。durvalumab 的安全性特征与总体人群和已知的 durvalumab 安全性特征基本一致。 结论:对于 EGFRm 肿瘤患者,durvalumab 的 PFS 和 OS 结果与安慰剂相似,置信区间较宽。由于患者数量较少,且缺乏根据肿瘤生物标志物状态评估临床结局的前瞻性研究,这些数据应谨慎解读。需要进一步研究以确定不可切除 III 期 EGFRm NSCLC 的最佳治疗方法。
N Engl J Med. 2017-9-8
N Engl J Med. 2018-9-25
Nat Rev Clin Oncol. 2025-8-14
Cancers (Basel). 2025-5-30
Transl Lung Cancer Res. 2025-3-31