Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Nov 7;11:9469-9481.
doi: 10.2147/CMAR.S218635. eCollection 2019.

A Molecular Epidemiological Analysis Of Programmed Cell Death Ligand-1 (PD-L1) Protein Expression, Mutations And Survival In Non-Small Cell Lung Cancer

Affiliations
Free PMC article

A Molecular Epidemiological Analysis Of Programmed Cell Death Ligand-1 (PD-L1) Protein Expression, Mutations And Survival In Non-Small Cell Lung Cancer

Matthew B Schabath et al. Cancer Manag Res. .
Free PMC article

Abstract

Purpose: To characterize programmed cell death ligand-1 (PD-L1) expression in relation to survival and gene mutation status in patients with advanced NSCLC. The study also explored the influence of tumor mutational burden (TMB) on PD-L1 expression and patient characteristics.

Patients and methods: Adult patients with histologically or cytologically documented Stage IIIB/Stage IV/recurrent/progressive NSCLC, Eastern Cooperative Oncology Group performance status 0 to 3, and >2 lines of prior systemic treatment regimens were included in this retrospective analysis. Patients were treated from 1997 to 2015 at H. Lee Moffitt Cancer Center and Research Institute, Tampa, or at 7 community centers across the United States. PD-L1 expression level was determined using the VENTANA PD-L1 (SP263) Assay. EGFR and KRAS mutation status and ALK rearrangements were determined by targeted DNA sequencing; these were obtained from clinical records where targeted DNA sequencing was not performed. TMB was calculated as the total number of somatic mutations per sample.

Results: From a total of 136 patients included in the study, 23.5% had tumors with high PD-L1 expression (≥25%). There were no significant differences in patient characteristics, overall survival (OS), and progression-free survival (PFS) between patients with high PD-L1 expression (median OS: 39.5 months; median PFS: 15.8 months) vs low PD-L1 expression (<25%; median OS: 38.1 months; median PFS: 18.6 months). PD-L1 expression level correlated (P=0.05) with TMB and was consistent with The Cancer Genome Atlas data.

Conclusion: In this retrospective analysis, survival outcomes of patients with advanced NSCLC were comparable by PD-L1 expression level. EGFR and KRAS mutation status were not found to be significantly associated with PD-L1 expression level, while TMB was weakly associated with PD-L1 expression level. Overall, PD-L1 expression level was not observed to be an independent prognostic biomarker in this cohort of patients with advanced NSCLC treated with chemotherapy.

Keywords: non-small cell lung cancer; patient outcomes; prognostic biomarker; tumor mutational burden.

Conflict of interest statement

Dr. Gray receives research grants and personal fees from AstraZeneca; research grants from Merck, Bristol Myers Squibb, and Genentech, during the conduct of the study. She is an advisor for AstraZeneca. She also reports research grants and personal fees from AstraZeneca and Genentech; research grants from Array, Merck, Epic Sciences, Bristol Myers Squibb, Boehringer Ingelheim, Trovagene, and Novartis; personal fees from Takeda, Eli Lilly, Celgene, and Janssen, outside of the submitted work. Drs. Dalvi, Midha, Shire, Walker, and Rigas are employees of AstraZeneca and hold stock in the company. Dr Brody is now a retiree and was an employee of AstraZeneca at the time of the study. Dr Potter was an employee of AstraZeneca at the time of the study and currently an AstraZeneca stockholder. Drs. Greenawalt and Lawrence were employees of AstraZeneca at the time of the study and are currently employed with Bristol-Myers Squibb, USA, and Novartis, Switzerland, respectively. Drs Dai and Crim are employees of M2Gen. Drs Kumar and Huntsman were employees of M2Gen at the time of the study. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
OS and PFS by PD-L1 expression level. (A) OS by PD-L1 expression ≥25% showing no significant association between PD-L1 expression level and OS (log-rank test, P=0.968). (B) PFS by PD-L1 expression ≥25% showing no significant association between PD-L1 expression level and PFS (log-rank test, P=0.714). (C) OS by PD-L1 expression ≥25% showing no significant association between PD-L1 expression level and OS for patients receiving second-line therapies (log-rank test, P=0.523). (D) OS from third-line therapy by PD-L1 expression ≥25% showing no significant association between PD-L1 expression level and OS for patients receiving third-line systemic therapies (log-rank test, P=0.607). X-axis is in years. The analyses are censored at 5 years. Abbreviations: OS, overall survival; PD-L1, programmed cell death ligand-1; PFS, progression-free survival.
Figure 2
Figure 2
Mutational load vs PD-L1 expression level. (A) Scatter plot of log TMB and the percentage of tumor cells with PD-L1 expression demonstrating correlation between mutational load and % PD-L1 staining. PD-L1 expression, as a continuous covariate, was weakly but positively associated with the number of somatic mutations (Pearson’s correlation coefficient=0.22, P=0.05). (B) Correlation between mutational load and % PD-L1 staining in the TCGA demonstrating similar results as in Figure 2A. (C) Mutational load by high vs low PD-L1 expression level demonstrating no significant difference observed when TMB was analyzed by PD-L1 expression ≥25%. Abbreviations: PD-L1, programmed cell death ligand-1; TCGA, The Cancer Genome Atlas; TMB, tumor mutational burden.

Similar articles

See all similar articles

Cited by 1 article

References

    1. American Cancer Society. Cancer Facts & Figures 2018. Atlanta: American Cancer Society; 2018.
    1. American Cancer Society. Non-small cell lung cancer survival rates, by stage. 2018. Available from: https://www.cancer.org/cancer/non-small-cell-lung-cancer/detection-diagnosis-staging/survival-rates.html Accessed April 2018.
    1. Santarpia M, Giovannetti E, Rolfo C, et al. Recent developments in the use of immunotherapy in non-small cell lung cancer. Expert Rev Respir Med. 2016;10(7):781–798. doi:10.1080/17476348.2016.1182866 - DOI - PubMed
    1. Tchekmedyian N, Gray JE, Creelan BC, et al. Propelling immunotherapy combinations into the clinic. Oncology (Williston Park). 2015;29(12):990–1002. - PubMed
    1. Brahmer JR. Harnessing the immune system for the treatment of non-small-cell lung cancer. J Clin Oncol. 2013;31(8):1021–1028. doi:10.1200/JCO.2012.45.8703 - DOI - PubMed

Grant support

The study was funded by AstraZeneca. The sponsor was involved in the study design; collection, analysis, and interpretation of data; report writing; and the decision to submit.
Feedback