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Title: Programmed Cell Death Ligand 1 Expression in Untreated EGFR Mutated Advanced NSCLC and Response to Osimertinib Versus Comparator in FLAURA.
Austin Authors: Brown, Helen;Vansteenkiste, Johan;Nakagawa, Kazuhiko;Cobo, Manuel;John, Thomas ;Barker, Craig;Kohlmann, Alexander;Todd, Alexander;Saggese, Matilde;Chmielecki, Juliann;Markovets, Aleksandra;Scott, Marietta;Ramalingam, Suresh S
Affiliation: Precision Medicine, Oncology R&D, AstraZeneca, Cambridge, United Kingdom
Respiratory Oncology Unit (Respiratory Diseases), University Hospital KU Leuven, Leuven, Belgium
Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka, Japan
Medical Oncology Department, University Regional Hospital of Málaga, IBIMA, Málaga, Spain
Precision Medicine, Oncology R&D, AstraZeneca, Cambridge, United Kingdom
Oncology Biometrics, Oncology, AstraZeneca, Cambridge, United Kingdom
Global Medicines Development, Oncology, AstraZeneca, Cambridge, United Kingdom
Translational Medicine, Oncology, AstraZeneca, Waltham, Massachusetts
Precision Medicine, Oncology R&D, AstraZeneca, Cambridge, United Kingdom
Emory University School of Medicine, Winship Cancer Institute, Atlanta, Georgia.
Olivia Newton-John Cancer Research Institute
Austin Health
Issue Date: Jan-2020
Date: 2019-10-09
Publication information: Journal of Thoracic Oncology 2020; 15(1): 138-143
Abstract: EGFR mutated (EGFRm) NSCLC tumors occasionally express programmed cell death ligand 1 (PD-L1), although frequency and clinical relevance are not fully characterized. We report PD-L1 expression in patients with EGFRm advanced NSCLC and association with clinical outcomes following treatment with osimertinib or comparator EGFR tyrosine kinase inhibitors in the FLAURA trial (phase III, NCT02296125). Of 231 tissue blocks available from the screened population (including EGFRm-positive and -negative samples), 197 had sufficient tissue for PD-L1 testing using the SP263 (Ventana, Tucson, Arizona) immunohistochemical assay. Tumor cell (TC) staining thresholds of PD-L1 TC greater than or equal to 1%, TC greater than or equal to 25%, and TC greater than or equal to 50% were applied. Progression-free survival (PFS) was investigator-assessed, per Response Evaluation Criteria in Solid Tumor, version 1.1, according to PD-L1 expressors (TC ≥ 1%) or negatives (TC < 1%) in randomized patients. PD-L1 staining was successful in 193 of 197 patient formalin-fixed paraffin-embedded blocks; of these, 128 of 193 were EGFRm-positive and 106 of 128 patients were randomized to treatment (osimertinib: 54; comparator: 52). At the PD-L1 TC greater than or equal to 25% threshold, 8% (10 of 128) of EGFRm-positive tumors expressed PD-L1 versus 35% (23 of 65) of EGFRm-negative tumors. With the TC greater than or equal to 1% threshold, 51% (65 of 128) versus 68% (44 of 65) were mutation-positive and -negative, respectively, and with the TC greater than or equal to 50% threshold, 5% (7 of 128) versus 28% (18 of 65), were mutation-positive and -negative, respectively. For PD-L1 expressors (TC ≥ 1%), median PFS was 18.4 months with osimertinib and 6.9 months with comparator (hazard ratio = 0.30; 95% confidence interval: 0.15-0.60). For PD-L1-negative patients (TC < 1%), median PFS was 18.9 months with osimertinib and 10.9 months with comparator (hazard ratio = 0.37; 95% confidence interval: 0.17-0.74). Clinical benefit with osimertinib was unaffected by PD-L1 expression status.
DOI: 10.1016/j.jtho.2019.09.009
Journal: Journal of Thoracic Oncology
PubMed URL: 31605792
Type: Journal Article
Subjects: EGFR mutated
Programmed death ligand 1
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