Comprehensive assessment of PD-L1 expression, tumor mutational burden and oncogenic driver alterations in non-small cell lung cancer patients treated with immune checkpoint inhibitors,Lung Cancer

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Comprehensive assessment of PD-L1 expression, tumor mutational burden and oncogenic driver alterations in non-small cell lung cancer patients treated with immune checkpoint inhibitors
Lung Cancer ( IF 4.5 ) Pub Date : 2021-07-26 , DOI: 10.1016/j.lungcan.2021.07.015
Kiyotaka Yoh ₁ , Shingo Matsumoto ₁ , Naoki Furuya ₂ , Kazumi Nishino ₃ , Shingo Miyamoto ₄ , Satoshi Oizumi ₅ , Norio Okamoto ₆ , Hidetoshi Itani ₇ , Shoichi Kuyama ₈ , Atsushi Nakamura ₉ , Koichi Nishi ₁₀ , Ikue Fukuda ₁₁ , Koji Tsuta ₁₂ , Yuichiro Hayashi ₁₃ , Noriko Motoi ₁₄ , Genichiro Ishii ₁₅ , Koichi Goto ₁

Affiliation

Department of Thoracic Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.
Division of Respiratory Medicine, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan.
Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan.
Department of Medical Oncology, Japanese Red Cross Medical Center, Tokyo, Japan.
Department of Respiratory Medicine, National Hospital Organization Hokkaido Cancer Center, Sapporo, Japan.
Department of Thoracic Oncology and Bronchology, Osaka Habikino Medical Center, Habikino, Japan.
Department of Respiratory Medicine, Japanese Red Cross Ise Hospital, Ise, Japan.
Department of Respiratory Medicine, Iwakuni Clinical Center, Iwakuni, Japan.
Department of Pulmonary Medicine, Sendai Kousei Hospital, Sendai, Japan.
Division of Respiratory Medicine, Ishikawa Prefecutual Central Hospital, Kanazawa, Japan.
Department of Pulmonary Medicine, Itami City Hospital, Hyogo, Japan.
Department of Pathology and Laboratory Medicine, Kansai Medical University, Osaka, Japan.
Department of Anatomic Pathology, International University of Health and Welfare Narita Hospital, Narita, Japan.
Department of Diagnostic Pathology, National Cancer Center Hospital, Tokyo, Japan.
Department of Pathology and Clinical Laboratories, National Cancer Center Hospital East, Kashiwa, Japan.

Objectives

Immune checkpoint inhibitors (ICIs) have proven to be effective treatment for lung cancer. However, a precise predictive immuno-oncology biomarker is still under development. We investigated the associations among PD-L1 expression, tumor mutational burden (TMB), and oncogenic driver alterations in advanced non-small cell lung cancer (NSCLC) patients treated with ICIs.

Materials and methods

This multicenter cohort study included 1017 lung cancer patients. PD-L1 expression using four IHC assays (22C3, 28-8, SP263, SP142), TMB by whole-exome sequencing and oncogenic driver alterations were analyzed comprehensively. Clinical characteristics, treatment and survival data were collected.

Results

The results of 22C3 and 28–8 for PD-L1 expression showed acceptable concordance (k = 0.89; 95% confidence interval [CI], 0.87–0.92), and the clinical outcomes of ICIs classified according to PD-L1 expression by both assays were also approximately the same. There was slight concordance (k = 0.16; 95% CI, 0.11–0.22) between 22C3 and SP142, and high PD-L1 expression by SP142 was correspond to very high PD-L1 expressions by other assays. Patients with both high PD-L1 expression and high TMB showed a good response to ICIs with the response rate of 64% and median progression-free survival of 9.0 months despite of small population. Common EGFR or STK11 mutations showed a lower rate of high PD-L1 expression and a worse efficacy of ICIs and KRAS mutations had no negative impact on response to ICIs.

Conclusion

Comprehensive assessment of PD-L1 expression, TMB, and oncogenic driver alterations would help to better predict the clinical outcomes of ICIs in NSCLC patients.

中文翻译：

免疫检查点抑制剂治疗非小细胞肺癌患者PD-L1表达、肿瘤突变负荷和致癌驱动改变的综合评估

目标

免疫检查点抑制剂 (ICIs) 已被证明是治疗肺癌的有效方法。然而，精确的预测性免疫肿瘤生物标志物仍在开发中。我们研究了接受 ICI 治疗的晚期非小细胞肺癌 (NSCLC) 患者的 PD-L1 表达、肿瘤突变负荷 (TMB) 和致癌驱动程序改变之间的关联。

材料和方法

这项多中心队列研究包括 1017 名肺癌患者。使用四种 IHC 检测（22C3、28-8、SP263、SP142）的 PD-L1 表达、全外显子组测序的 TMB 和致癌驱动程序改变进行了全面分析。收集了临床特征、治疗和生存数据。

结果

22C3 和 28-8 PD-L1 表达的结果显示出可接受的一致性（k = 0.89；95% 置信区间 [CI]，0.87-0.92），并且两种检测根据 PD-L1 表达分类的 ICI 的临床结果也大致相同。22C3 和 SP142 之间存在轻微的一致性（k = 0.16；95% CI，0.11-0.22），SP142 的高 PD-L1 表达对应于其他检测的非常高的 PD-L1 表达。PD-L1 高表达和 TMB 高的患者对 ICI 的反应良好，反应率为 64%，中位无进展生存期为 9.0 个月，尽管人群较少。常见的EGFR或STK11突变显示出较低的高 PD-L1 表达率和较差的 ICI 和KRAS疗效突变对 ICI 的反应没有负面影响。