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
| Autor: | Atsushi Nakamura, Yuichiro Hayashi, Ikue Fukuda, Satoshi Oizumi, Koichi Nishi, Kazumi Nishino, Koichi Goto, Noriko Motoi, Naoki Furuya, Norio Okamoto, Shoichi Kuyama, Koji Tsuta, Genichiro Ishii, Shingo Matsumoto, Shingo Miyamoto, Hidetoshi Itani, Kiyotaka Yoh |
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| Rok vydání: | 2021 |
| Předmět: |
Pulmonary and Respiratory Medicine
Oncology Cancer Research medicine.medical_specialty Lung Neoplasms Concordance medicine.medical_treatment Population STK11 medicine.disease_cause B7-H1 Antigen Cohort Studies Carcinoma Non-Small-Cell Lung Internal medicine medicine Humans education Lung cancer Immune Checkpoint Inhibitors education.field_of_study business.industry Immunotherapy medicine.disease Immunohistochemistry Biomarker (medicine) KRAS business |
| Zdroj: | Lung Cancer. 159:128-134 |
| ISSN: | 0169-5002 |
| DOI: | 10.1016/j.lungcan.2021.07.015 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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