Impact of Patient Characteristics, Prior Therapy, and Sample Type on Tumor Cell Programmed Cell Death Ligand 1 Expression in Patients with Advanced NSCLC Screened for the ATLANTIC Study

Anne Marie Boothman, Marietta Scott, Marianne Ratcliffe, Jessica Whiteley, Phillip A. Dennis, Catherine Wadsworth, Alan Sharpe, Naiyer A. Rizvi, Marina Chiara Garassino, Jill Walker

Research output: Contribution to journalArticle

Abstract

Introduction: We evaluated the impact of patient characteristics, sample types, and prior non-immunotherapy treatment on tumor cell (TC) programmed cell death ligand 1 (PD-L1) expression using samples from patients with advanced NSCLC. Methods: Patients (N = 1590) screened for the ATLANTIC study submitted a recently acquired (≤3 months) or archival (>3 months to >3 years old) tumor sample for PD-L1 assessment using the VENTANA PD-L1 (SP263) Assay with a cutoff of ≥25% of TCs expressing PD-L1 (TC ≥25%). Samples were acquired either before or after the two or more treatment regimens required for study entry and sample age varied among patients. A subset of patients (n = 123) provided both recent and archival samples. Results: A total of 517 of 1590 (32.5%) patients had TC greater than or equal to 25%: prevalence was greater in smokers versus nonsmokers (p = 0.0005) and those with EGFR− versus EGFR+ tumors (p = 0.0002); these effects were independent. Prevalence of TC greater than or equal to 25% was increased in recent metastatic versus primary (p = 0.005) and recent versus archival (p = 0.039) samples. Chemotherapy or radiotherapy, but not tyrosine kinase inhibition, before sampling was associated with significantly increased PD-L1 prevalence. PD-L1 status (TC ≥25% cutoff) remained unchanged in 74.0% of patients with recent and archival samples; where PD-L1 status changed, it was more likely to increase than decrease over time or with intervening treatment. Conclusions: Several factors potentially impact PD-L1 TC greater than or equal to 25% prevalence in advanced NSCLC; however, no characteristic can be considered a surrogate for PD-L1 expression. Fresh biopsy may provide more accurate assessment of current tumoral PD-L1 expression where a low/negative result is seen in an archival sample, especially if the patient has received intervening therapy.

Original languageEnglish
Pages (from-to)1390-1399
Number of pages10
JournalJournal of Thoracic Oncology
Volume14
Issue number8
DOIs
Publication statusPublished - Aug 2019

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Cell Death
Ligands
Neoplasms
Therapeutics
Protein-Tyrosine Kinases
Radiotherapy
Biopsy
Drug Therapy

Keywords

  • Diagnostic test
  • Immunohistochemistry
  • Immunotherapy
  • NSCLC
  • Programmed cell death ligand 1

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

Impact of Patient Characteristics, Prior Therapy, and Sample Type on Tumor Cell Programmed Cell Death Ligand 1 Expression in Patients with Advanced NSCLC Screened for the ATLANTIC Study. / Boothman, Anne Marie; Scott, Marietta; Ratcliffe, Marianne; Whiteley, Jessica; Dennis, Phillip A.; Wadsworth, Catherine; Sharpe, Alan; Rizvi, Naiyer A.; Garassino, Marina Chiara; Walker, Jill.

In: Journal of Thoracic Oncology, Vol. 14, No. 8, 08.2019, p. 1390-1399.

Research output: Contribution to journalArticle

Boothman, Anne Marie ; Scott, Marietta ; Ratcliffe, Marianne ; Whiteley, Jessica ; Dennis, Phillip A. ; Wadsworth, Catherine ; Sharpe, Alan ; Rizvi, Naiyer A. ; Garassino, Marina Chiara ; Walker, Jill. / Impact of Patient Characteristics, Prior Therapy, and Sample Type on Tumor Cell Programmed Cell Death Ligand 1 Expression in Patients with Advanced NSCLC Screened for the ATLANTIC Study. In: Journal of Thoracic Oncology. 2019 ; Vol. 14, No. 8. pp. 1390-1399.
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abstract = "Introduction: We evaluated the impact of patient characteristics, sample types, and prior non-immunotherapy treatment on tumor cell (TC) programmed cell death ligand 1 (PD-L1) expression using samples from patients with advanced NSCLC. Methods: Patients (N = 1590) screened for the ATLANTIC study submitted a recently acquired (≤3 months) or archival (>3 months to >3 years old) tumor sample for PD-L1 assessment using the VENTANA PD-L1 (SP263) Assay with a cutoff of ≥25{\%} of TCs expressing PD-L1 (TC ≥25{\%}). Samples were acquired either before or after the two or more treatment regimens required for study entry and sample age varied among patients. A subset of patients (n = 123) provided both recent and archival samples. Results: A total of 517 of 1590 (32.5{\%}) patients had TC greater than or equal to 25{\%}: prevalence was greater in smokers versus nonsmokers (p = 0.0005) and those with EGFR− versus EGFR+ tumors (p = 0.0002); these effects were independent. Prevalence of TC greater than or equal to 25{\%} was increased in recent metastatic versus primary (p = 0.005) and recent versus archival (p = 0.039) samples. Chemotherapy or radiotherapy, but not tyrosine kinase inhibition, before sampling was associated with significantly increased PD-L1 prevalence. PD-L1 status (TC ≥25{\%} cutoff) remained unchanged in 74.0{\%} of patients with recent and archival samples; where PD-L1 status changed, it was more likely to increase than decrease over time or with intervening treatment. Conclusions: Several factors potentially impact PD-L1 TC greater than or equal to 25{\%} prevalence in advanced NSCLC; however, no characteristic can be considered a surrogate for PD-L1 expression. Fresh biopsy may provide more accurate assessment of current tumoral PD-L1 expression where a low/negative result is seen in an archival sample, especially if the patient has received intervening therapy.",
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T1 - Impact of Patient Characteristics, Prior Therapy, and Sample Type on Tumor Cell Programmed Cell Death Ligand 1 Expression in Patients with Advanced NSCLC Screened for the ATLANTIC Study

AU - Boothman, Anne Marie

AU - Scott, Marietta

AU - Ratcliffe, Marianne

AU - Whiteley, Jessica

AU - Dennis, Phillip A.

AU - Wadsworth, Catherine

AU - Sharpe, Alan

AU - Rizvi, Naiyer A.

AU - Garassino, Marina Chiara

AU - Walker, Jill

PY - 2019/8

Y1 - 2019/8

N2 - Introduction: We evaluated the impact of patient characteristics, sample types, and prior non-immunotherapy treatment on tumor cell (TC) programmed cell death ligand 1 (PD-L1) expression using samples from patients with advanced NSCLC. Methods: Patients (N = 1590) screened for the ATLANTIC study submitted a recently acquired (≤3 months) or archival (>3 months to >3 years old) tumor sample for PD-L1 assessment using the VENTANA PD-L1 (SP263) Assay with a cutoff of ≥25% of TCs expressing PD-L1 (TC ≥25%). Samples were acquired either before or after the two or more treatment regimens required for study entry and sample age varied among patients. A subset of patients (n = 123) provided both recent and archival samples. Results: A total of 517 of 1590 (32.5%) patients had TC greater than or equal to 25%: prevalence was greater in smokers versus nonsmokers (p = 0.0005) and those with EGFR− versus EGFR+ tumors (p = 0.0002); these effects were independent. Prevalence of TC greater than or equal to 25% was increased in recent metastatic versus primary (p = 0.005) and recent versus archival (p = 0.039) samples. Chemotherapy or radiotherapy, but not tyrosine kinase inhibition, before sampling was associated with significantly increased PD-L1 prevalence. PD-L1 status (TC ≥25% cutoff) remained unchanged in 74.0% of patients with recent and archival samples; where PD-L1 status changed, it was more likely to increase than decrease over time or with intervening treatment. Conclusions: Several factors potentially impact PD-L1 TC greater than or equal to 25% prevalence in advanced NSCLC; however, no characteristic can be considered a surrogate for PD-L1 expression. Fresh biopsy may provide more accurate assessment of current tumoral PD-L1 expression where a low/negative result is seen in an archival sample, especially if the patient has received intervening therapy.

AB - Introduction: We evaluated the impact of patient characteristics, sample types, and prior non-immunotherapy treatment on tumor cell (TC) programmed cell death ligand 1 (PD-L1) expression using samples from patients with advanced NSCLC. Methods: Patients (N = 1590) screened for the ATLANTIC study submitted a recently acquired (≤3 months) or archival (>3 months to >3 years old) tumor sample for PD-L1 assessment using the VENTANA PD-L1 (SP263) Assay with a cutoff of ≥25% of TCs expressing PD-L1 (TC ≥25%). Samples were acquired either before or after the two or more treatment regimens required for study entry and sample age varied among patients. A subset of patients (n = 123) provided both recent and archival samples. Results: A total of 517 of 1590 (32.5%) patients had TC greater than or equal to 25%: prevalence was greater in smokers versus nonsmokers (p = 0.0005) and those with EGFR− versus EGFR+ tumors (p = 0.0002); these effects were independent. Prevalence of TC greater than or equal to 25% was increased in recent metastatic versus primary (p = 0.005) and recent versus archival (p = 0.039) samples. Chemotherapy or radiotherapy, but not tyrosine kinase inhibition, before sampling was associated with significantly increased PD-L1 prevalence. PD-L1 status (TC ≥25% cutoff) remained unchanged in 74.0% of patients with recent and archival samples; where PD-L1 status changed, it was more likely to increase than decrease over time or with intervening treatment. Conclusions: Several factors potentially impact PD-L1 TC greater than or equal to 25% prevalence in advanced NSCLC; however, no characteristic can be considered a surrogate for PD-L1 expression. Fresh biopsy may provide more accurate assessment of current tumoral PD-L1 expression where a low/negative result is seen in an archival sample, especially if the patient has received intervening therapy.

KW - Diagnostic test

KW - Immunohistochemistry

KW - Immunotherapy

KW - NSCLC

KW - Programmed cell death ligand 1

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