免疫治疗转移性非小细胞肺癌临床试验中反应率和无进展生存期与总生存期的相关性：FDA 汇总分析。
Correlations of response rate and progression-free survival with overall survival in immunotherapy trials for metastatic non-small-cell lung cancer: an FDA pooled analysis.
机构信息
Office of Oncologic Diseases, Food and Drug Administration, Silver Spring, MD, USA.
Office of Biostatistics, Food and Drug Administration, Silver Spring, MD, USA.
出版信息
Lancet Oncol. 2024 Apr;25(4):455-462. doi: 10.1016/S1470-2045(24)00040-8. Epub 2024 Mar 5.
BACKGROUND
Radiographic changes might not fully capture the treatment effects of immune checkpoint inhibitors (ICIs). We aimed to assess correlations of overall response rate and progression-free survival with overall survival in trials of ICIs for metastatic non-small-cell lung cancer (NSCLC).
METHODS
To assess trial-level and patient-level correlations of overall response rate and progression-free survival with overall survival, we conducted a pooled analysis of first-line randomised trials (including patients aged ≥18 years with metastatic squamous and non-squamous NSCLC and an Eastern Cooperative Oncology Group performance status of 0-1) submitted to the US Food and Drug Administration from June 24, 2016, to March 16, 2021. Eligible trials evaluated at least one ICI in the experimental group versus chemotherapy in the control group. At the trial level, we used weighted linear regression to derive coefficients of determination (R). At the patient level, we used Cox proportional hazards models to compare overall survival between responders versus non-responders per Response Evaluation Criteria in Solid Tumours (version 1.1).
FINDINGS
A total of 13 trials including 9285 patients evaluated ICIs alone or in combination with chemotherapy versus chemotherapy alone. At the trial level, the R was 0·61 (95% CI 0·32-0·84) for correlation of overall response rate with overall survival and 0·70 (0·40-0·89) for correlation of progression-free survival with overall survival. Correlations ranged from weak to moderate when evaluating subgroups by PD-L1 expression and were consistent across trials evaluating ICIs alone or in combination with chemotherapy. At the patient level, responders had longer overall survival than non-responders (hazard ratio [HR] 0·28 [95% CI 0·26-0·30]). Among responders, overall survival was longer in patients enrolled in experimental groups than in control groups (HR 0·54 [95% CI 0·48-0·61]).
INTERPRETATION
Correlations of overall response rate and progression-free survival with overall survival were generally moderate in this pooled analysis. The findings support routine analysis of mature overall survival data, where feasible, in first-line randomised trials of ICIs for metastatic NSCLC.
FUNDING
US Food and Drug Administration.
背景
影像学改变可能无法完全捕捉免疫检查点抑制剂（ICI）的治疗效果。我们旨在评估转移性非小细胞肺癌（NSCLC）ICI 临床试验中总缓解率和无进展生存期与总生存期的相关性。
方法
为了评估一线随机试验中总缓解率和无进展生存期与总生存期的试验水平和患者水平相关性，我们对 2016 年 6 月 24 日至 2021 年 3 月 16 日向美国食品和药物管理局提交的一线随机试验（包括年龄≥18 岁的转移性鳞状和非鳞状 NSCLC 患者，东部合作肿瘤学组表现状态为 0-1）进行了汇总分析。合格的试验评估了实验组中至少一种 ICI 与对照组中的化疗相比。在试验水平上，我们使用加权线性回归来得出决定系数（R）。在患者水平上，我们使用 Cox 比例风险模型来比较根据实体瘤反应评估标准（版本 1.1），每例应答者与无应答者的总生存期。
结果
共有 13 项试验，包括 9285 例患者，评估了 ICI 单药或联合化疗与化疗相比的疗效。在试验水平上，总缓解率与总生存期的相关性 R 为 0.61（95%CI 0.32-0.84），无进展生存期与总生存期的相关性 R 为 0.70（0.40-0.89）。当按 PD-L1 表达评估亚组时，相关性从弱到中度不等，并且在评估 ICI 单药或联合化疗的试验中一致。在患者水平上，应答者的总生存期长于无应答者（风险比[HR]0.28[95%CI 0.26-0.30]）。在应答者中，实验组患者的总生存期长于对照组（HR 0.54[95%CI 0.48-0.61]）。
解释
在本汇总分析中，总缓解率和无进展生存期与总生存期的相关性通常为中度。这些发现支持在转移性 NSCLC 的 ICI 一线随机试验中，在可行的情况下，对成熟的总生存期数据进行常规分析。
资金来源
美国食品和药物管理局。
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