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Tumor Mutation Burden as a Potential Biomarker for PD-1/PD-L1 Inhibition in Advanced Non-small Cell Lung Cancer

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Abstract

Background

Immunotherapy based on programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors has revolutionized the treatment of non-small cell lung cancer (NSCLC). Patients with high PD-L1 expression or DNA mismatch repair deficiency (dMMR)/microsatellite instability-high (MSI-H) cancer are reported to benefit from PD-1/PD-L1 inhibitors. However, additional biomarkers are needed, and whether tumor mutation burden (TMB) can be a robust biomarker or not is still controversial.

Objective

We conducted this study to assess TMB as a biomarker for PD-1/PD-L1 inhibitor treatment in advanced NSCLC patients in a real-world setting.

Patients and Methods

Chinese NSCLC patients who received a PD-1/PD-L1 inhibitor at the People’s Liberation Army General Hospital and who had pathological tissues available for TMB were retrospectively analyzed. Demographic and clinical information were evaluated. Targeted next-generation sequencing (NGS) of the tumor tissue was performed. The relationship between TMB and clinical benefit was assessed.

Results

Thirty-four patients treated with PD-1/PD-L1 inhibitors between March 2015 and January 2019 were analyzed. The TMB was greater in patients with complete response (CR)/partial response (PR) versus stable disease (SD) versus progressive disease (PD) (median 11 vs. 9.7 vs. 4.2 mutations/megabase [Mb]; p = 0.049). The median progression-free survival was 10.6 months in the TMB-high group versus 3.9 months in the TMB-low group (cut-off value = 10 mutations/Mb) (hazard ratio [HR] 0.26 [95% confidence interval 0.12–0.57], p = 0.0007). The median overall survival was 21.0 months and 11.6 months (HR 0.37 [0.17–0.81], p = 0.0126) in the TMB-high group and the TMB-low group, respectively. The disease control rate was higher in the TMB-high group than in the TMB-low group (100% vs. 70%, p = 0.024).

Conclusions

High TMB was associated with a better outcome in advanced NSCLC patients who received PD-1/PD-L1 inhibitors in China. Further studies are needed to confirm our findings.

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Availability of Data and Material

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We thank the patients and their families, and thank Professor Hu for providing guidance and coaching.

Author information

Authors and Affiliations

  1. School of Medicine, Nankai University, 94 Weijin Road, Nankai, Tianjin, 300071, People’s Republic of China

    Di Huang, Ziwei Huang, Zhaozhen Wu & Yi Hu

  2. Department of Medical Oncology, Chinese People’s Liberation Army General Hospital, 28 Fuxing Road, Haidian, Beijing, 100853, People’s Republic of China

    Di Huang, Fan Zhang, Haitao Tao, Sujie Zhang, Junxun Ma, Jinliang Wang, Zhefeng Liu, Pengfei Cui, Shixue Chen, Ziwei Huang, Zhaozhen Wu, Lei Zhao & Yi Hu

  3. Department of Graduate Administration, Chinese PLA General Hospital, Beijing, People’s Republic of China

    Pengfei Cui & Shixue Chen

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  1. Di Huang
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Contributions

DH served as first author, as the primary contributor to the manuscript. DH had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. All authors contributed to the study’s concept and design. All authors contributed to the acquisition, analysis, and interpretation of data. All authors took responsibility for the manuscript’s drafting and revision. Critical revision of the manuscript for important intellectual content was undertaken by YH; statistical analysis by DH and HT; and study supervision by YH and FZ. All authors agree to be accountable for all aspects of the work and for ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Yi Hu.

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Funding

This work was supported by the National Key R&D Program of China (No. 2017YFC0907900/2017YFC0907904).

Conflict of interest

Di Huang, Fan Zhang, Haitao Tao, Sujie Zhang, Junxun Ma, Jinliang Wang, Zhefeng Liu, Pengfei Cui, Shixue Chen, Ziwei Huang, Zhaozhen Wu, Lei Zhao, and Yi Hu declare that they have no conflicts of interest that might be relevant to the contents of this article.

Ethics approval and consent to participate

The study was approved by the institutional review board of the People’s Liberation Army General Hospital, Beijing, China (approval number: S2018-092-01). Written informed consent was provided by all patients involved in this study.

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Huang, D., Zhang, F., Tao, H. et al. Tumor Mutation Burden as a Potential Biomarker for PD-1/PD-L1 Inhibition in Advanced Non-small Cell Lung Cancer. Targ Oncol 15, 93–100 (2020). https://doi.org/10.1007/s11523-020-00703-3

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  • DOI: https://doi.org/10.1007/s11523-020-00703-3

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