OncoTargets and Therapy (Aug 2020)
High PD-L1 Expression is Associated with Unfavorable Clinical Outcome in EGFR-Mutated Lung Adenocarcinomas Treated with Targeted Therapy
Abstract
Byung Woo Yoon,1,2 Boksoon Chang,3 Seung Hyeun Lee3 1Department of Internal Medicine, Seoul Paik Hospital, Seoul, South Korea; 2Department of Internal Medicine, Inje University College of Medicine, Gimhae, South Korea; 3Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, South KoreaCorrespondence: Seung Hyeun LeeDivision of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Kyung Hee University School of Medicine, Kyungheedae-Ro 23, Dongdaemun-Gu, Seoul 02447, South KoreaTel +82 2 958 8511Fax +82 2 968 1848Email [email protected]: Although programmed death-ligand 1 (PD-L1) expression is widely accepted as a predictive and prognostic biomarker in immunotherapy, its implications in lung cancer patients with driving mutations are still unclear. The objective of this study is to determine the association between PD-L1 expression and treatment outcome in epidermal growth factor receptor (EGFR)-mutated lung cancer treated with tyrosine kinase inhibitors (TKIs).Methods: We retrospectively enrolled EGFR-mutant, advanced lung adenocarcinoma patients who received first-line EGFR-TKIs and evaluated the PD-L1 tumor proportion score (TPS) using the 22C3 pharmDx assay. We investigated the distribution of patients with different PD-L1 TPS values, followed by the analysis of response rate (RR), survival rate, and incidence of secondary T790M mutation according to the PD-L1 TPS group.Results: Among the 131 patients analyzed, the proportion of patients with PD-L1 TPS ≥ 50%, 1– 49%, and < 1%, was 17.6%, 32.8%, and 49.6%, respectively. The RR was significantly lower in the group with PD-L1 TPS ≥ 50% than in the other groups (43.5% vs 72.1% vs 78.5%, all p = 0.001). In multivariate analysis, PD-L1 TPS ≥ 50% was independently associated with a significantly shorter PFS in the overall population (hazard ratio [HR] = 2.64, p = 0.004) and associated with shorter OS in patients with exon 19 deletion (HR = 2.55, p = 0.041) compared with PD-L1 TPS < 50%. In addition, the frequency of secondary T790M mutation after TKI failure was significantly lower in the group with PD-L1 TPS ≥ 50% than in the other groups (13.3% vs 40.0% vs 53.3%, all p = 0.001). PD-L1 TPS ≥ 50% was an independent predictor of a lower frequency of this mutation (HR = 0.63, p = 0.043).Conclusion: High PD-L1 expression was associated with unfavorable clinical outcome and less development of secondary T790M mutation, suggesting a distinct subgroup warranting active surveillance and tailored therapeutic approach.Keywords: lung cancer, programmed death-ligand 1, epidermal growth factor receptor mutation, tyrosine kinase inhibitor, clinical outcome, prognosis, T790M
