Temporal evolution of programmed death-ligand 1 expression in patients with non-small cell lung cancer
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Background/Aims: Programmed death-ligand 1 (PD-L1) expression, a validated predictive biomarker for anti-PD-1/PD-L1 inhibitors, is reported to change over time. This poses challenges during clinical application in non-small cell lung cancer. Methods: This study included patients with non-small cell lung cancer who underwent surgery or biopsy and evaluation of PD-L1 expression in tumor cells via immunohistochemistry more than twice. We set the threshold of PD-L1 positivity to 10% and categorized patients into four groups according to changes in PD-L1 expression. Clinicopathologic information was collected from medical records. Statistical analyses, including Fisher’s exact test and log-rank test, were performed. Results: Of 109 patients, 38 (34.9%) and 45 (41.3%) had PD-L1 positivity in archival and recent samples, respectively. PD-L1 status was maintained in 78 (71.6%) patients, but changed in 31 (28.4%), with 19 (17.4%) from negative to positive. There were no significant differences in characteristics between patients who maintained PD-L1 negativity and whose PD-L1 status changed from negative to positive. Patients harboring PD-L1 positivity in either archival or recent samples achieved better responses (p = 0.129) and showed longer overall survival than those who maintained PD-L1 negativity when they received immune checkpoint inhibitors after platinum failure (median overall survival 14.4 months vs. 4.93 months; hazard ratio, 0.43; 95% confidence interval, 0.20 to 0.93). Conclusions: PD-L1 status changed in about one-fourth of patients. PD-L1 positivity in either archival or recent samples was predictive of better responses to immune checkpoint inhibitors. Therefore, archival samples could be used for assessment of PD-L1 status. The need for new biopsies should be decided individually.
Abstract
Background/Aims: Programmed death-ligand 1 (PD-L1) expression, a validated predictive biomarker for anti-PD-1/PD-L1 inhibitors, is reported to change over time. This poses challenges during clinical application in non-small cell lung cancer. Methods: This study included patients with non-small cell lung cancer who underwent surgery or biopsy and evaluation of PD-L1 expression in tumor cells via immunohistochemistry more than twice. We set the threshold of PD-L1 positivity to 10% and categorized patients into four groups according to changes in PD-L1 expression. Clinicopathologic information was collected from medical records. Statistical analyses, including Fisher’s exact test and log-rank test, were performed. Results: Of 109 patients, 38 (34.9%) and 45 (41.3%) had PD-L1 positivity in archival and recent samples, respectively. PD-L1 status was maintained in 78 (71.6%) patients, but changed in 31 (28.4%), with 19 (17.4%) from negative to positive. There were no significant differences in characteristics between patients who maintained PD-L1 negativity and whose PD-L1 status changed from negative to positive. Patients harboring PD-L1 positivity in either archival or recent samples achieved better responses (p = 0.129) and showed longer overall survival than those who maintained PD-L1 negativity when they received immune checkpoint inhibitors after platinum failure (median overall survival 14.4 months vs. 4.93 months; hazard ratio, 0.43; 95% confidence interval, 0.20 to 0.93). Conclusions: PD-L1 status changed in about one-fourth of patients. PD-L1 positivity in either archival or recent samples was predictive of better responses to immune checkpoint inhibitors. Therefore, archival samples could be used for assessment of PD-L1 status. The need for new biopsies should be decided individually.
참고문헌 (30)
- Pardoll DM, "The blockade of immune checkpoints in cancer immunotherapy", Nat Rev Cancer, 12, pp.252~264 (2012)
- Borghaei H, "Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer", N Engl J Med, 373, pp.1627~1639 (2015)
- Herbst RS, "Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer(KEYNOTE-010) : a randomised controlled trial", Lancet, 387, pp.1540~1550 (2016)
- Gibney GT, "Predictive biomarkers for checkpoint inhibitor-based immunotherapy", Lancet Oncol, 17, pp.e542~e551 (2016)
- Topalian SL, "Safety, activity, and immune correlates of anti-PD-1 antibody in cancer", N Engl J Med, 366, pp.2443~2454 (2012)
- Ock CY, "Pan-cancer immunogenomic perspective on the tumor microenvironment based on PD-L1 and CD8 T-cell infiltration", Clin Cancer Res, 22, pp.2261~2270 (2016)
- Rizvi NA, "Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer", Science, 348, pp.124~128 (2015)
- Rooney MS, "Molecular and genetic properties of tumors associated with local immune cytolytic activity", Cell, 160, pp.48~61 (2015)
- Ayers M, "IFN-γ-related mRNA profile predicts clinical response to PD-1 blockade", J Clin Invest, 127, pp.2930~2940 (2017)
- Ock CY, "Genomic landscape associated with potential response to anti-CTLA-4 treatment in cancers", Nat Commun, 8, pp.1050~ (2017)
- Cho JH, "Programmed death ligand 1 expression in paired non-small cell lung cancer tumor samples", Clin Lung Cancer, 18, pp.e473~e479 (2017)
- Sheng J, "Expression of programmed death ligand-1 on tumor cells varies pre and post chemotherapy in non-small cell lung cancer", Sci Rep, 6, pp.20090~ (2016)
- Herbst RS, "Use of archival versus newly collected tumor samples for assessing PDL1 expression and overall survival : an updated analysis of KEYNOTE-010 trial", Ann Oncol, 30, pp.281~289 (2019)
- Eisenhauer EA, "New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)", Eur J Cancer, 45, pp.228~247 (2009)
- Topalian SL, "Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy", Nat Rev Cancer, 16, pp.275~287 (2016)
- Zhang N, "The EGFR pathway is involved in the regulation of PD-L1 expression via the IL-6", JAK, Int J Oncol, pp.2016, 49[DOI]
- Ota K, "Induction of PD-L1expression by the EML4-ALK oncoprotein and downstream signaling pathways in non-small cell lung cancer", Clin Cancer Res, 21, pp.4014~4021 (2015)
- Scheel AH, "PD-L1 expression in non-small cell lung cancer : correlations with genetic alterations", Oncoimmunology, 5, pp.e1131379~ (2016)
- Ock CY, "Changes in programmed death-ligand 1 expression during cisplatin treatment in patients with head and neck squamous cell carcinoma", Oncotarget, 8, pp.97920~97927 (2017)
- 신정훈, "Effect of Platinum-Based Chemotherapy on PD-L1 Expression on Tumor Cells in Non-small Cell Lung Cancer", Cancer Research and Treatment, 51(3), pp.1086~1097 (2019), 대한암학회
- Han JJ, "Change in PD-L1 expression after acquiring resistance to gefitinib in EGFR-mutant non-small-cell lung cancer", Clin Lung Cancer, 17, pp.263~270 (2016)
- Illidge T, "Radiation therapy induces an adaptive upregulation of PD-L1 on tumor cells which may limit the efficacy of the anti-tumor immune response but can be circumvented by anti-PD-L1", Int J Radiat Oncol Biol Phys, 90(1 Suppl), pp.S776~ (2014)
- Ilie M, "Comparative study of the PD-L1 status between surgically resected specimens and matched biopsies of NSCLC patients reveal major discordances : a potential issue for anti-PD-L1 therapeutic strategies", Ann Oncol, 27, pp.147~153 (2016)
- Bigras G, "Small biopsies misclassify up to 35% of PD-L1 assessments in advanced lung non-small cell lung carcinomas", Appl Immunohistochem Mol Morphol, 26, pp.701~708 (2018)
- Kim H, "PD-L1 immunohistochemical assays for assessment of therapeutic strategies involving immune checkpoint inhibitors in non-small cell lung cancer : a comparative study", Oncotarget, 8, pp.98524~98532 (2017)
- Zhou J, "Programmed death ligand 1 expression and CD8+ tumor-infiltrating lymphocyte density differences between paired primary and brain metastatic lesions in non-small cell lung cancer", Biochem Biophys Res Commun, 498, pp.751~757 (2018)
- Kim S, "Comparative analysis of PDL1expression between primary and metastatic pulmonary adenocarcinomas", Eur J Cancer, 75, pp.141~149 (2017)
- Hirsch FR, "PD-L1 immunohistochemistry assays for lung cancer : results from phase 1 of the blueprint PD-L1 IHC assay comparison project", J Thorac Oncol, 12, pp.208~222 (2017)
- Scheel AH, "Harmonized PD-L1 immunohistochemistry for pulmonary squamous-cell and adenocarcinomas", Mod Pathol, 29, pp.1165~1172 (2016)
- Ratcliffe MJ, "Agreement between programmed cell death ligand-1 diagnostic assays across multiple protein expression cutoffs in non-small cell lung cancer", Clin Cancer Res, 23, pp.3585~3591 (2017)