P1.01-57 Association of Initial PD-L1 Expression with T790M-Acquired Resistance in Advanced EGFR-Mutant Lung Adenocarcinoma Patients

Abstract

The primary objective was to investigate the association between initial programmed cell death-ligand 1 (PD-L1) expression levels and the frequency of T790M-acquired resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase Inhibitor (TKI) in patients with advanced EGFR-mutant lung adenocarcinoma. We examined patients with advanced EGFR-mutant lung adenocarcinoma whose initial PD-L1 expression levels and T790M-acquired mutation status after EGFR-TKI failure (gefitinib, erlotinib or afatinib) could be evaluated. We retrospectively investigated the patients’ characteristics and survival, as well as the association between initial PD-L1 expression levels and frequency of T790M-acquired resistance Overall, 100 patients were enrolled. Nine (9%) patients had an initial PD-L1 tumor proportion score (TPS) of ≥50%, 19(19%) had PD-L1 TPS of 1%-49%, and 72 (72%) had PD-L1 TPS of <1%. T790M-acquired mutation (T790M+) was identified in 57 (57%) patients. Initial PD-L1 expression levels were not associated with the frequency of T790M-acquired mutations in patients (p=0.822). Positive PD-L1 expression (PD-L1+) was associated with lower OS compared with negative PD-L1 expression (PD-L1-) (median overall survival [OS], 40.3 vs 74.3 months, p=0.0053). Furthermore, T790M+ was associated with longer OS compared with T790M- in total and PD-L1- population (total: median OS, 74.3 vs 41.3 months, p=0.0154, PD-L1-: median OS, 82.0 vs 41.2 months, p=0.00412), but not in PD-L1+ population (median OS, 36.2 vs 46.2 months, p=0.792). Among 57 patients with T790M-aquired mutation, 49 received osimertinib treatment. The estimated median progression-free survival rate of osimertinib was 13.2 months in PD-L1- patients (n=37) and 6.9 months in PD-L1+ patients (n=12) (p=0.224). There was no association between initial PD-L1 expression levels and the frequency of T790M-aquired mutations in patients. However, PD-L1+ expression levels in patients with treatment-naïve advanced EGFR-mutant lung adenocarcinoma predicted poorer outcomes. Intriguingly, T790M-aquired mutations were related to longer OS in PD-L1- patients, but not in PD-L1+. Thus, for patients with T790M-acquired mutant and initial PD-L1 positive lung adenocarcinoma in whom the use of osimertinib is indicated, other treatment options should be considered without hesitation if the treatment effects are not as expected.