Nakahama Kenji, Osawa Masahiko, Izumi Motohiro, Yoshimoto Naoki, Sugimoto Akira, Nagamine Hiroaki, Ogawa Koichi, Matsumoto Yoshiya, Sawa Kenji, Tani Yoko, Kaneda Hiroyasu, Mitsuoka Shigeki, Watanabe Tetsuya, Asai Kazuhisa, Kawaguchi Tomoya
Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka, Japan.
Department of Diagnostic Pathology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan.
Transl Lung Cancer Res. 2022 Dec;11(12):2438-2451. doi: 10.21037/tlcr-22-496.
It remains unclear whether assessing programmed death-ligand 1 (PD-L1) expression by SP142 plus 22C3 adds value for predicting the response to immunotherapy in non-small cell lung cancer (NSCLC).
This retrospective multicenter study included patients with advanced NSCLC treated with immune-checkpoint inhibitors. We constructed tissue microarrays (TMAs) and performed immunohistochemical staining with 22C3 and SP142 assays. We denoted the PD-L1 tumor proportion score (TPS) obtained from clinical medical records based on 22C3 staining as "22C3 (C)" and that obtained with 22C3 staining using our TMA as "22C3 (TMA)". SP142 staining was evaluated in both tumor cells and immune cells. We assessed the concordance between each PD-L1 assessment method and analyzed the objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) based on the PD-L1 expression level determined using the 22C3 and SP142 assays.
In total, 288 patients were included. Among those with 22C3 (TMA) ≥50%, 60% of patients showed SP142 TC3 or IC3; among patients with 22C3 (C) <1%, 9% and 18% exhibited 22C3 (TMA) ≥1% and SP142 TC1/2/3 or IC1/2/3, respectively. Among patients with 22C3 (C) ≥50% treated with immune-checkpoint inhibitor monotherapy, the SP142 TC1/2/3 or IC1/2/3 group showed significantly better ORR, PFS and OS than the SP142 TC0 and IC0 group (54% 29%, P=0.040, median =11.0 3.2 months, P=0.002, median =27.9 12.6 months, P=0.030, respectively). Multivariate analysis revealed that SP142 TC0 and IC0 was an independent unfavorable prognostic factor for PFS and OS in patients with 22C3 (C) ≥50% treated with immune-checkpoint inhibitor monotherapy. For those with 22C3 (C) ≥50% and SP142 TC0 and IC0, immune-checkpoint inhibitor concurrent with chemotherapy tended to result in a longer PFS and OS than immune-checkpoint inhibitor monotherapy (median =13.7 2.3 months, P=0.054, median = not estimable 12.0 months, P=0.064, respectively).
SP142 evaluation contributes to the prediction of immune-checkpoint inhibitor efficacy in NSCLC with high PD-L1 expression assessed by 22C3.
通过SP142和22C3评估程序性死亡配体1（PD-L1）表达是否能为预测非小细胞肺癌（NSCLC）免疫治疗反应增添价值仍不清楚。
这项回顾性多中心研究纳入了接受免疫检查点抑制剂治疗的晚期NSCLC患者。我们构建了组织微阵列（TMA），并使用22C3和SP142检测进行免疫组织化学染色。我们将基于22C3染色从临床病历中获得的PD-L1肿瘤比例评分（TPS）记为“22C3（C）”，将使用我们的TMA进行22C3染色获得的记为“22C3（TMA）”。对肿瘤细胞和免疫细胞均进行SP142染色评估。我们评估了每种PD-L1评估方法之间的一致性，并基于使用22C3和SP142检测确定的PD-L1表达水平分析客观缓解率（ORR）、无进展生存期（PFS）和总生存期（OS）。
总共纳入了288例患者。在22C3（TMA）≥50%的患者中，60%的患者显示SP142 TC3或IC3；在22C3（C）<1%的患者中，分别有9%和18%的患者22C3（TMA）≥1%以及SP142 TC1/2/3或IC1/2/3。在接受免疫检查点抑制剂单药治疗且22C3（C）≥50%的患者中，SP142 TC1/2/3或IC1/2/3组的ORR、PFS和OS显著优于SP142 TC0和IC0组（分别为54%对29%，P = 0.040；中位值 = 11.0对3.2个月，P = 0.002；中位值 = 27.9对12.6个月，P = 0.030）。多变量分析显示，在接受免疫检查点抑制剂单药治疗且22C3（C）≥50%的患者中，SP142 TC0和IC0是PFS和OS的独立不良预后因素。对于22C3（C）≥50%且SP142 TC0和IC0的患者，免疫检查点抑制剂联合化疗相比于免疫检查点抑制剂单药治疗往往导致更长的PFS和OS（中位值分别为13.7对2.3个月，P = 0.054；中位值为不可估计对12.0个月，P = 0.064）。
SP142评估有助于预测通过22C3评估的高PD-L1表达的NSCLC中免疫检查点抑制剂的疗效。
