Impact of EGFR mutation on the clinical efficacy of PD-1 inhibitors in patients with pulmonary adenocarcinoma

• Published in: Journal of cancer research and clinical oncology 2019-05, Vol.145 (5), p.1341-1349
• Main Authors: Cho, Jang Ho, Jung, Hyun Ae, Lee, Se-Hoon, Ahn, Jin Seok, Ahn, Myung-Ju, Park, Keunchil, Sun, Jong-Mu
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Cancer Research; Cell death; Epidermal growth factor receptors; Hematology; Internal Medicine; Lung cancer; Medicine; Medicine & Public Health; Multivariate analysis; Mutation; Oncology; Original Article – Clinical Oncology; PD-1 protein; PD-L1 protein; Smoking; Tumors
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-019-02889-0

Purpose We evaluated the predictive role of EGFR mutation on the efficacy of PD-1/PD-L1 inhibitor therapy in patients with advanced pulmonary adenocarcinoma while considering clinical factors such as PD-L1 expression, gender, and smoking status. Methods Patients were required to have available data for EGFR mutation, PD-L1 expression, and efficacy of PD-1/PD-L1 inhibitors. Results Among 178 patients with EGFR-mutant ( n  = 38) or wild-type (WT) ( n  = 140) tumors, the EGFR mutation group had a lower objective response rate (ORR) (15.8% vs. 32.9%, p  = 0.04) than the EGFR WT group, similar to the pattern observed for other factors: weak/negative PD-L1 expression vs. strong PD-L1 expression (17.3% vs. 39.2%, p  = 0.001); never smokers vs. smokers (19.4% vs. 35.1%, p  = 0.03); and females vs. males (21.0% vs. 33.6%, p  = 0.08). EGFR mutation and weak/negative PD-L1 expression were associated with a significantly shorter median PFS than EGFR WT (1.9 vs. 3.0 months, p  = 0.04) and strong PD-L1 expression (1.6 vs. 3.9 months, p  = 0.007), respectively. In multivariate analysis, EGFR mutation predicted worse ORR [hazard ratio (HR) 3.15; 95% confidence interval (CI) 1.15–8.63] and PFS (HR 1.75, 95% CI 1.11–2.75), as did weak/negative PD-L1 expression (ORR, HR 3.46, 95% CI 1.62–7.37; and PFS, HR 1.72, 95% CI 1.17–2.53). Conclusions Together with PD-L1 expression, EGFR mutation status is an important factor to predict the efficacy of PD-1/PD-L1 inhibitors in patients with pulmonary adenocarcinoma.