Department of Radiation Oncology, National University Cancer Institute, Singapore; National University Hospital, Singapore; National University Health System, Singapore; National University of Singapore, Singapore.
Acta Oncol. 2020 Dec;59(12):1430-1437. doi: 10.1080/0284186X.2020.1807600. Epub 2020 Aug 24.
To determine the impact of programed death-ligand 1 (PD-L1) expression on progression-free survival (PFS) outcomes in stage IV epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) treated with first-line EGFR tyrosine kinase inhibitors (TKIs).
We searched biomedical databases for studies comparing PFS outcomes of PD-L1-positive versus (vs) PD-L1-negative tumors. We assessed the methodological quality of eligible studies using ROBINS-I tool. We employed a two-staged meta-analysis approach by reconstructing individual patient data of each study from the published Kaplan-Meier curves and then pooling the individual hazard ratios (HRs) and weighted mean differences (WMDs) for restricted mean PFS time at 6 (RMPFST6) and 12 (RMPFST12) months using random-effect models. We assessed the quality of summarized evidence using GRADE approach.
We identified five non-randomized comparative studies including 435 patients. The overall risk of bias in the methodological quality of included studies was moderate. PD-L1-positive tumors were associated with significantly worse PFS outcomes compared to PD-L1-negative tumors (HR: 2.41, 95% confidence interval (CI): 1.59-3.66, < .001; WMD in RMPFST6: -1.01, 95% CI: -1.65 to -0.37, = .002; WMD in RMPFST12: -2.64, 95% CI: -4.40 to -0.88, = .003). Subgroup analysis showed that the effect of PD-L1 expression on PFS outcomes was greater for studies using older-generation rather than third-generation TKIs (HR: 2.69 vs 1.22, = .069; WMD in RMPFST6: -1.23 vs -0.07, = .005; WMD in RMPFST12: -3.29 vs -0.12, = .003). The quality of summarized evidence was judged to be low.
There is low certainty in the evidence to suggest that positive PD-L1 expression is associated with inferior disease control and survival outcomes in patients with stage IV EGFR-mutated NSCLC treated with first-line EGFR TKIs.
为了确定程序性死亡配体 1（PD-L1）表达对接受一线表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）治疗的 IV 期 EGFR 突变非小细胞肺癌（NSCLC）患者无进展生存期（PFS）结局的影响。
我们在生物医学数据库中搜索了比较 PD-L1 阳性与（vs）PD-L1 阴性肿瘤患者 PFS 结局的研究。我们使用 ROBINS-I 工具评估了合格研究的方法学质量。我们采用两阶段荟萃分析方法，通过从已发表的 Kaplan-Meier 曲线重建每个研究的个体患者数据，然后使用随机效应模型汇总 6 个月（RMPFST6）和 12 个月（RMPFST12）时受限平均 PFS 时间的个体风险比（HR）和加权均数差值（WMD）。我们使用 GRADE 方法评估汇总证据的质量。
我们确定了五项非随机比较研究，包括 435 名患者。纳入研究的方法学质量整体偏倚风险为中度。与 PD-L1 阴性肿瘤相比，PD-L1 阳性肿瘤的 PFS 结局明显更差（HR：2.41，95%置信区间（CI）：1.59-3.66， < .001；RMPFST6 时的 WMD：-1.01，95% CI：-1.65 至 -0.37， = .002；RMPFST12 时的 WMD：-2.64，95% CI：-4.40 至 -0.88， = .003）。亚组分析表明，PD-L1 表达对 PFS 结局的影响在使用第一代而非第三代 TKI 的研究中更大（HR：2.69 比 1.22， = .069；RMPFST6 时的 WMD：-1.23 比 -0.07， = .005；RMPFST12 时的 WMD：-3.29 比 -0.12， = .003）。汇总证据的质量被判断为低。
有低确定性证据表明，在接受一线 EGFR TKI 治疗的 IV 期 EGFR 突变 NSCLC 患者中，PD-L1 阳性与疾病控制和生存结局较差相关。
