Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan; Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Lung Cancer. 2018 Apr;118:36-40. doi: 10.1016/j.lungcan.2018.01.024. Epub 2018 Feb 2.
Expression of programmed cell death-ligand 1 (PD-L1) has been associated with clinical outcome of programmed cell death-1 (PD-1) pathway blockade in non-small cell lung cancer (NSCLC). The PD-L1 IHC 22C3 pharmDx assay, the only companion diagnostic for pembrolizumab therapy, has revealed that ∼30% of all NSCLCs express PD-L1 at a high level. The frequency of high PD-L1 expression in NSCLCs with known driver oncogenes has remained unclear, however.
We retrospectively evaluated PD-L1 expression with the 22C3 assay in tumor tissue of 80 lung adenocarcinoma patients including 71 with EGFR mutations and 9 with ALK rearrangements, all of whom were treated with corresponding tyrosine kinase inhibitors (TKIs).
Of the 80 tumors analyzed, 26 (32.5%) had a PD-L1 tumor proportion score (TPS) of 1%-49% and 9 (11.3%) had a PD-L1 TPS of ≥50%; 35 (43.8%) thus had a PD-L1 TPS of ≥1%. Of the 71 tumors with EGFR mutations, 23 (32.4%) had a PD-L1 TPS of 1%-49% and 7 (9.9%) had a PD-L1 TPS of ≥50%. A PD-L1 TPS of ≥1% was not associated with any clinical characteristic examined. Progression-free survival on initial TKI treatment was significantly poorer for patients with a PD-L1 TPS of ≥1% than for those with a PD-L1 TPS of <1% (p = .016).
A subset of patients with EGFR mutations or ALK rearrangements had a PD-L1 TPS of ≥50%. Prospective studies are thus warranted to examine the efficacy of PD-1/PD-L1 inhibitors in such patients.
程序性死亡配体 1（PD-L1）的表达与非小细胞肺癌（NSCLC）中程序性死亡-1（PD-1）通路阻断的临床结果相关。PD-L1 IHC 22C3 pharmDx 检测是 pembrolizumab 治疗的唯一伴随诊断方法，该检测方法显示，约 30%的所有 NSCLC 以高表达水平表达 PD-L1。然而，具有已知驱动致癌基因的 NSCLC 中高 PD-L1 表达的频率仍不清楚。
我们回顾性地评估了 80 例肺腺癌患者肿瘤组织中 22C3 检测的 PD-L1 表达情况，其中 71 例患者存在 EGFR 突变，9 例患者存在 ALK 重排，所有患者均接受了相应的酪氨酸激酶抑制剂（TKI）治疗。
在分析的 80 个肿瘤中，26 个（32.5%）肿瘤比例评分（TPS）为 1%-49%，9 个（11.3%）TPS 为≥50%；因此，35 个（43.8%）肿瘤的 TPS 为≥1%。在 71 例存在 EGFR 突变的肿瘤中，23 个（32.4%）TPS 为 1%-49%，7 个（9.9%）TPS 为≥50%。PD-L1 TPS≥1%与检查的任何临床特征均无关。初始 TKI 治疗时，PD-L1 TPS≥1%的患者无进展生存期明显差于 TPS<1%的患者（p=0.016）。
一部分 EGFR 突变或 ALK 重排的患者 PD-L1 TPS≥50%。因此，有必要开展前瞻性研究，以检验此类患者中 PD-1/PD-L1 抑制剂的疗效。
