MA11.07 Efficacy of Immune-Checkpoint Inhibitors and EGFR-TKIs in NSCLC Patients with High PD-L1 Expression

Recently, several studies have demonstrated that patients with non-small cell lung carcinoma (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations show poor clinical outcomes in response to treatment with anti-programmed cell death-1 (PD-1) inhibitors. Conversely, EGFR tyrosine kinase inhibitors (EGFR-TKIs) are not effective in NSCLC showing high programmed death ligand 1 (PD-L1) expression levels. In this study, we retrospectively investigated the relationship between high PD-L1 expression and the efficacy of PD-1 inhibitors and EGFR-TKIs in patients with NSCLC. The subjects of this study were patients with NSCLC who had received treatment with PD-1 inhibitors at the National Cancer Center Hospital between March 2017 and December 2018. The PD-L1 expression in the tumor cells was divided into two groups based on the tumor proportion score (TPS): <50% (low) and ≥50% (high). Of the 414 patients treated with PD-1 inhibitors, the 263 patients in whom the PD-L1 expression levels could be evaluated were considered as being eligible for inclusion in this study. Among the 153 patients with high PD-L1 expression, we assessed the efficacy of PD-1 inhibitors according to the EGFR mutation status. The objective response rate (ORR) was 29.4% (95% confidence interval [CI], 1.3 to 53.1) in the EGFR-mutated patients and 43.4% (95% CI, 35.4 to 51.8) in the EGFR wild-type patients. The median progression-free survival (PFS) was 5.3 months (95% CI, 1.3 to 12.4) in the EGFR-mutated patients and 8.3 months (95% CI, 6.0 to 11.7) in the EGFR wild-type patients (hazard Ratio [HR] = 0.62; 95% CI, 0.62 to 1.14). A total of 33 patients received EGFR-TKI therapy. We assessed the efficacy of EGFR-TKIs according to the PD-L1 expression level. The ORR was 50.0% (95% CI, 28.0 to 72.0) in the high PD-L1 expression group and 52.9% (95% CI, 31.0 to 73.8) in the low PD-L1 expression group. The median PFS was 18.8 months (95% CI, 2.8 to 35.7) in the high PD-L1 expression group and 12.7 months (95% CI, 7.2 to 20.9) in the low PD-L1 expression group (HR = 0.83; 95% CI, 0.38 to 1.81).Tabled 1PD-L1 High EGFR+PD-L1 High EGFR−PD-L1 Low EGFR+PD-L1 Low EGFR−Total N171361892Median age, years (range)62 (47–85)62 (33–87)64.5 (37–83)62 (33–83)Sex (n) Female Male7 1036 10015 325 67ECOG PS (n) 0, 1 214 3125 1116 281 11Smoking history (n) Never-smoker Smoker7 1021 11512 613 79EGFR mutation status (n) Ex 19 del L858R Others7 6 413 2 3ICI agent used (n) Pembrolizumab Nivolumab11 6105 314 1421 71Line of ICI therapy (n) First-line Second-line Third-line or more2 3 1285 42 95 64 230 2 16Efficasy ORR (%) PD-1 inhibitors EGFR-TKIs PFS (months) PD-1 inhibitors EGFR-TKIs29.4 50.0 5.3 18.843.4 8.30 52.9 1.6 12.716.3 3.8 Open table in a new tab Even in a population of NSCLC patients showing high PD-L1 expression, the efficacy of PD-1 inhibitors tended to be lower in the EGFR-mutated patients as compared to the EGFR wild-type patients. In regard to EGFR-mutated patients with a PD-L1 TPS of ≥50%, our findings suggested that high PD-L1 expression might not predict a poor efficacy of EGFR-TKIs.