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.

Abstract

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.

• Authors: Kiyotaka Yoh, Shingo Matsumoto, Naoki Furuya, Kazumi Nishino, Shingo Miyamoto, Satoshi Oizumi, Norio Okamoto, Hidetoshi Itani, Shoichi Kuyama, Atsushi Nakamura, Koichi Nishi, Ikue Fukuda, Koji Tsuta, Yuichiro Hayashi, Noriko Motoi, Genichiro Ishii, Koichi Goto
• Journal: Lung cancer (Amsterdam, Netherlands) (Lung Cancer) Vol. 159 Pg. 128-134 (09 2021) ISSN: 1872-8332 [Electronic] Ireland
• PMID: 34333203 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• B7-H1 Antigen
• Immune Checkpoint Inhibitors

Topics

• B7-H1 Antigen (genetics)
• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics)
• Cohort Studies
• Humans
• Immune Checkpoint Inhibitors
• Lung Neoplasms (drug therapy, genetics)