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Epidermal growth factor receptor mutated (EGFRm) non-small cell lung cancer (NSCLC) tumors occasionally express programmed cell death ligand 1 (PD-L1), though 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) immunohistochemical assay. Tumor cell (TC) staining thresholds of PD-L1 TC≥1%, TC≥25% and TC≥50% were applied. Progression-free survival (PFS) was investigator-assessed, per RECIST 1.1, according to PD-L1 expressors (TC≥1%) or negatives (TC<1%) in randomized patients. PD-L1 staining was successful in 193/197 patient FFPE blocks; of these 128/193 were EGFRm positive and 106/128 patients were randomized to treatment (osimertinib: 54; comparator: 52). At PD-L1 TC≥25% threshold, 8% (10/128) of EGFRm positive tumors expressed PD-L1 versus 35% (23/65) of EGFRm negative tumors. With TC≥1% threshold, 51% (65/128) versus 68% (44/65) were mutation positive and negative respectively, and with the TC≥50% threshold, 5% (7/128) versus 28% (18/65), 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 (HR 0.30 [95% CI: 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 (HR 0.37 [95% CI: 0.17-0.74]). Clinical benefit with osimertinib was unaffected by PD-L1 expression status. |
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