Anne-Marie Boothman1, Marietta Scott2, Marianne Ratcliffe2, Jessica Whiteley2, Phillip A Dennis3, Catherine Wadsworth4, Alan Sharpe5, Naiyer A Rizvi6, Marina Chiara Garassino7, Jill Walker2. 1. Precision Medicine and Genomics, IMED Biotech Unit, AstraZeneca, Cambridge, United Kingdom. Electronic address: Anne-Marie.Boothman@astrazeneca.com. 2. Precision Medicine and Genomics, IMED Biotech Unit, AstraZeneca, Cambridge, United Kingdom. 3. Global Medicines Development, AstraZeneca, Gaithersburg, Maryland. 4. Global Medicines Development, AstraZeneca, Alderley Park, United Kingdom. 5. Discovery Sciences, IMED Biotech Unit, AstraZeneca, Cambridge, United Kingdom. 6. Division of Hematology and Oncology, Columbia University Medical Center, New York, New York. 7. Thoracic Oncology Unit, Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
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.
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-L1TC 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.
Authors: Deborah Blythe Doroshow; Sheena Bhalla; Mary Beth Beasley; Lynette M Sholl; Keith M Kerr; Sacha Gnjatic; Ignacio I Wistuba; David L Rimm; Ming Sound Tsao; Fred R Hirsch Journal: Nat Rev Clin Oncol Date: 2021-02-12 Impact factor: 66.675
Authors: A J Schoenfeld; H Rizvi; C Bandlamudi; J L Sauter; W D Travis; N Rekhtman; A J Plodkowski; R Perez-Johnston; P Sawan; A Beras; J V Egger; M Ladanyi; K C Arbour; C M Rudin; G J Riely; B S Taylor; M T A Donoghue; M D Hellmann Journal: Ann Oncol Date: 2020-02-06 Impact factor: 32.976
Authors: Torben Steiniche; Sun Young Rha; Hyun Cheol Chung; Jeanette Baehr Georgsen; Morten Ladekarl; Marianne Nordsmark; Marie Louise Jespersen; Hyo Song Kim; Hyunki Kim; Carly Fein; Laura H Tang; Ting Wu; Matthew J Marton; Senaka Peter; David P Kelsen; Geoffrey Ku Journal: Cancer Med Date: 2021-10-24 Impact factor: 4.452