INTRODUCTION Epidermal growth factor receptor mutated (EGFRm) non-small cell lung cancer (NSCLC) tumors occasionally express programmed cell death ligand 1 (PD-L1), though frequency and clinical-relevance are not fully characterized. We report PD-L1 expression in patients with EGFRm advanced NSCLC and association with clinical outcomes following treatment with osimertinib or comparator EGFR tyrosine kinase inhibitors in the FLAURA trial (phase III, NCT02296125). METHODS Of 231 tissue blocks available from the screened population (including EGFRm positive and negative samples), 197 had sufficient tissue for PD-L1 testing using the SP263 (Ventana) immunohistochemical assay. Tumor cell (TC) staining thresholds of PD-L1 TC≥1%, TC≥25% and TC≥50% were applied. Progression-free survival (PFS) was investigator-assessed, per RECIST 1.1, according to PD-L1 expressors (TC≥1%) or negatives (TC<1%) in randomized patients. RESULTS PD-L1 staining was successful in 193/197 patient FFPE blocks; of these 128/193 were EGFRm positive and 106/128 patients were randomized to treatment (osimertinib: 54; comparator: 52). At PD-L1 TC≥25% threshold, 8% (10/128) of EGFRm positive tumors expressed PD-L1 versus 35% (23/65) of EGFRm negative tumors. With TC≥1% threshold, 51% (65/128) versus 68% (44/65) were mutation positive and negative respectively, and with the TC≥50% threshold, 5% (7/128) versus 28% (18/65), were mutation positive and negative, respectively. For PD-L1 expressors (TC≥1%), median PFS was 18.4 months with osimertinib and 6.9 months with comparator (HR 0.30 [95% CI: 0.15-0.60]). For PD-L1 negative patients (TC<1%), median PFS was 18.9 months with osimertinib and 10.9 months with comparator (HR 0.37 [95% CI: 0.17-0.74]). CONCLUSIONS Clinical benefit with osimertinib was unaffected by PD-L1 expression status.

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简要报告：未治疗的 EGFR 突变晚期非小细胞肺癌中程序性细胞死亡配体 1 的表达以及对奥希替尼的反应与 FLAURA 中的比较剂

引言 表皮生长因子受体突变 (EGFRm) 非小细胞肺癌 (NSCLC) 肿瘤偶尔会表达程序性细胞死亡配体 1 (PD-L1)，但频率和临床相关性尚未完全确定。我们在 FLAURA 试验（III 期，NCT02296125）中报告了 EGFRm 晚期 NSCLC 患者的 PD-L1 表达以及与奥希替尼或比较 EGFR 酪氨酸激酶抑制剂治疗后临床结果的相关性。方法 从筛选人群（包括 EGFRm 阳性和阴性样本）中获得的 231 个组织块中，197 个有足够的组织用于使用 SP263 (Ventana) 免疫组织化学测定法进行 PD-L1 检测。肿瘤细胞（TC）染色阈值采用PD-L1 TC≥1%、TC≥25%和TC≥50%。根据 RECIST 1.1，研究者评估了无进展生存期 (PFS)，根据随机患者的 PD-L1 表达（TC≥1%）或阴性（TC<1%）。结果 PD-L1 染色在 193/197 例患者 FFPE 块中成功；其中 128/193 例 EGFRm 阳性，106/128 例患者被随机分配接受治疗（奥希替尼：54；比较器：52）。在 PD-L1 TC≥25% 阈值时，8% (10/128) 的 EGFRm 阳性肿瘤表达 PD-L1，而 35% (23/65) 的 EGFRm 阴性肿瘤。TC≥1% 阈值时，51% (65/128) 和 68% (44/65) 分别为突变阳性和阴性，TC≥50% 阈值时，5% (7/128) 和 28% (18 /65），分别是突变阳性和阴性。对于 PD-L1 表达者 (TC≥1%)，奥希替尼组的中位 PFS 为 18.4 个月，比较组为 6.9 个月 (HR 0.30 [95% CI: 0.15-0.60])。对于 PD-L1 阴性患者（TC<1%），奥希替尼的中位 PFS 为 18.9 个月和 10 个月。9 个月与比较器 (HR 0.37 [95% CI: 0.17-0.74])。结论 奥希替尼的临床获益不受 PD-L1 表达状态的影响。