Introduction: This study evaluated whether tumor expression of programmed death ligand 1 (PD‐L1) could predict the response of EGFR‐mutated NSCLC to EGFR tyrosine kinase inhibitor (TKI) therapy. Methods: We retrospectively evaluated patients who received EGFR‐TKIs for advanced NSCLC at the Guangdong Lung Cancer Institute between April 2016 and September 2017 and were not enrolled in clinical studies. The patients' EGFR and PD‐L1 statuses were simultaneously evaluated. Results: Among the 101 eligible patients, strong PD‐L1 expression significantly decreased objective response rate, compared with weak or negative PD‐L1 expression (35.7% versus 63.2% versus 67.3%, p = 0.002), and shortened progression‐free survival (3.8 versus 6.0 versus 9.5 months, p < 0.001), regardless of EGFR mutation type (19del or L858R). Furthermore, positive PD‐L1 expression was predominantly observed among patients with de novo resistance rather than acquired resistance to EGFR‐TKIs (66.7% versus 30.2%, p = 0.009). Notably, we found a high proportion of PD‐L1 and cluster of differentiation 8 (CD8) dual‐positive cases among patients with de novo resistance (46.7%, 7 of 15). Finally, one patient with de novo resistance to EGFR‐TKIs and PD‐L1 and CD8 dual positivity experienced a favorable response to anti–programmed death 1 therapy. Conclusions: This study revealed the adverse effects of PD‐L1 expression on EGFR‐TKI efficacy, especially in NSCLC patients with de novo resistance. The findings indicate the reshaping of an inflamed immune phenotype characterized by PD‐L1 and CD8 dual positivity and suggest potential therapeutic sensitivity to programmed death 1 blockade.

中文翻译：

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强 PD-L1 表达可预测 EGFR 突变非小细胞肺癌患者对 EGFR TKI 的不良反应和新耐药

简介：本研究评估了程序性死亡配体 1 (PD-L1) 的肿瘤表达是否可以预测 EGFR 突变的 NSCLC 对 EGFR 酪氨酸激酶抑制剂 (TKI) 治疗的反应。方法：我们回顾性评估了 2016 年 4 月至 2017 年 9 月在广东省肺癌研究所接受 EGFR-TKI 治疗晚期 NSCLC 且未纳入临床研究的患者。同时评估患者的 EGFR 和 PD-L1 状态。结果：在 101 名符合条件的患者中，与弱或阴性 PD-L1 表达相比，强 PD-L1 表达显着降低客观缓解率（35.7% 对 63.2% 对 67.3%，p = 0.002），并缩短无进展生存期（ 3.8 个月对比 6.0 个月对比 9.5 个月，p < 0.001），无论 EGFR 突变类型（19del 或 L858R）如何。此外，阳性 PD-L1 表达主要在对 EGFR-TKI 有新发耐药而非获得性耐药的患者中观察到（66.7% 对 30.2%，p = 0.009）。值得注意的是，我们发现新发耐药患者中有很高比例的 PD-L1 和分化簇 8 (CD8) 双阳性病例（46.7%，15 人中有 7 人）。最后，一名对 EGFR-TKI 和 PD-L1 和 CD8 双阳性产生新耐药性的患者对抗程序性死亡 1 疗法产生了良好的反应。结论：本研究揭示了 PD-L1 表达对 EGFR-TKI 疗效的不利影响，尤其是在新发耐药的 NSCLC 患者中。研究结果表明，以 PD-L1 和 CD8 双阳性为特征的炎症免疫表型的重塑，并表明对程序性死亡 1 阻断具有潜在的治疗敏感性。