Programmed Cell Death Ligand 1 Expression in Untreated EGFR Mutated Advanced NSCLC and Response to Osimertinib Versus Comparator in FLAURA.

Abstract

INTRODUCTION:

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).

METHODS:

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.

RESULTS:

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).

CONCLUSIONS:

Clinical benefit with osimertinib was unaffected by PD-L1 expression status.

• Authors: Helen Brown, Johan Vansteenkiste, Kazuhiko Nakagawa, Manuel Cobo, Thomas John, Craig Barker, Alexander Kohlmann, Alexander Todd, Matilde Saggese, Juliann Chmielecki, Aleksandra Markovets, Marietta Scott, Suresh S Ramalingam
• Journal: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer (J Thorac Oncol) Vol. 15 Issue 1 Pg. 138-143 (01 2020) ISSN: 1556-1380 [Electronic] United States
• PMID: 31605792 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Chemical References

• Acrylamides
• Aniline Compounds
• Antineoplastic Agents
• B7-H1 Antigen
• Ligands
• osimertinib
• EGFR protein, human
• ErbB Receptors

Topics

• Acrylamides
• Aniline Compounds
• Antineoplastic Agents (therapeutic use)
• Apoptosis
• B7-H1 Antigen (genetics, therapeutic use)
• ErbB Receptors (genetics, therapeutic use)
• Humans
• Ligands
• Lung Neoplasms (drug therapy, genetics)
• Mutation