Abstract
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.
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Acknowledgements
This paper was supported by the following grant(s): the National R & D Program for Cancer Control, Ministry of Health and Welfare, Korea (1720180).
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All the procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional review board at Samsung Medical Center in Seoul, Korea, and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
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Supplementary Fig 1
. Correlation between PD-L1 expression as assessed by 22C3 PharmDx and SP263 antibodies (PDF 178 KB)
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Cho, J.H., Jung, H.A., Lee, SH. et al. Impact of EGFR mutation on the clinical efficacy of PD-1 inhibitors in patients with pulmonary adenocarcinoma. J Cancer Res Clin Oncol 145, 1341–1349 (2019). https://doi.org/10.1007/s00432-019-02889-0
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DOI: https://doi.org/10.1007/s00432-019-02889-0