Rangachari Deepa, VanderLaan Paul A, Shea Meghan, Le Xiuning, Huberman Mark S, Kobayashi Susumu S, Costa Daniel B
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
J Thorac Oncol. 2017 May;12(5):878-883. doi: 10.1016/j.jtho.2016.12.026. Epub 2017 Jan 16.
Targeted somatic genomic analysis (EGFR, anaplastic lymphoma receptor tyrosine kinase gene [ALK], and ROS1) and programmed death ligand 1 (PD-L1) tumor proportion score (TPS) determined by immunohistochemistry (IHC) are used for selection of first-line therapies in advanced lung cancer; however, the frequency of overlap of these biomarkers in routine clinical practice is poorly reported.
We retrospectively probed the first 71 pairs of patients with lung adenocarcinoma from our institution. They were analyzed for PD-L1 by IHC using the clone 22C3 pharmDx kit (Agilent Technologies, Santa Clara, CA) and evaluated for co-occurrence of genomic aberrations and clinicopathologic characteristics.
Surgical resection specimens, small biopsy (transbronchial or core needle) samples, and cytologic cell blocks (needle aspirates or pleural fluid) were tested. A PD-L1 TPS of at least ≥50% was seen in 29.6% of tumors. Of 19 tumors with EGFR mutations, ALK fluorescence in situ hybridization positivity, or ROS1 fluorescence in situ hybridization positivity, 18 had a PD-L1 TPS less than 50% versus only one tumor with a PD-L1 TPS of at least 50% (p = 0.0073). Tumors with a PD-L1 TPS of at least 50% were significantly associated with smoking status compared with tumors with a PD-L1 TPS less than 50% but were not associated with patient sex, ethnicity, tumor stage, biopsy site, or biopsy type/preparation.
PD-L1 IHC can be performed on routine clinical lung cancer specimens. A TPS of at least 50% seldom overlaps with presence of driver oncogenes with approved targeted therapies. Three biomarker-specified groups of advanced lung adenocarcinomas can now be defined, each paired with a specific palliative first-line systemic therapy of proven clinical benefit: (1) EGFR/ALK/ROS1-affected adenocarcinoma paired with a matched tyrosine kinase inhibitor (∼20% of cases), (2) PD-L1-enriched adenocarcinoma (TPS ≥50%) paired with anti-PD-1 pembrolizumab (∼30% of cases), and (3) biomarker-negative (i.e., EGFR/ALK/ROS1/PD-L1-negative) adenocarcinoma paired with platinum doublet chemotherapy with or without bevacizumab (∼50% of cases).
靶向体细胞基因组分析（表皮生长因子受体[EGFR]、间变性淋巴瘤激酶基因[ALK]和ROS1）以及通过免疫组织化学（IHC）测定的程序性死亡配体1（PD-L1）肿瘤比例评分（TPS）用于晚期肺癌一线治疗的选择；然而，在常规临床实践中这些生物标志物重叠的频率鲜有报道。
我们回顾性分析了来自本机构的前71对肺腺癌患者。使用克隆号为22C3的试剂（安捷伦科技公司，加利福尼亚州圣克拉拉）通过免疫组织化学对他们进行PD-L1分析，并评估基因组畸变的共现情况和临床病理特征。
对手术切除标本、小活检（经支气管或芯针活检）样本和细胞学细胞块（针吸活检或胸水）进行了检测。29.6%的肿瘤中观察到PD-L1 TPS至少≥50%。在19例有EGFR突变、ALK荧光原位杂交阳性或ROS1荧光原位杂交阳性的肿瘤中，18例的PD-L1 TPS小于50%，而只有1例肿瘤的PD-L1 TPS至少为50%（p = 0.0073）。与PD-L1 TPS小于50%的肿瘤相比，PD-L1 TPS至少为50%的肿瘤与吸烟状态显著相关，但与患者性别、种族、肿瘤分期、活检部位或活检类型/标本制备无关。
PD-L1免疫组织化学可在常规临床肺癌标本上进行。TPS至少为50%的情况很少与已获批靶向治疗的驱动癌基因的存在重叠。现在可以定义三组具有生物标志物特征的晚期肺腺癌，每组都与一种经证实具有临床益处的特定姑息性一线全身治疗方法相对应：（1）受EGFR/ALK/ROS1影响的腺癌与匹配的酪氨酸激酶抑制剂相对应（约20%的病例），（2）富含PD-L1的腺癌（TPS≥50%）与抗PD-1派姆单抗相对应（约30%的病例），以及（3）生物标志物阴性（即EGFR/ALK/ROS1/PD-L1阴性）的腺癌与含或不含贝伐单抗的铂类双联化疗相对应（约50%的病例）。
