P2.04-78 PD-L1 Expression as a Prognostic Marker for Non-Small Cell Lung Cancer in Distinct Mutational Status

Abstract

Programmed death-ligand 1 (PD-L1) expression is widely used as the predictive biomarker for immunotherapy treatment in NSCLC whereas their role as a prognostic marker is limited. Seventy-nine FFPE tissues (stage I-IV) during 2012-2017 were retrieved for Next Generation Sequencing (NGS) and immunohistochemistry (IHC) staining. PD-L1 expression was performed using 22C3 Ab. Positive-PD-L1 was defined by tumor proportion score (TPS) ≥1%. Targeted mutations and fusion genes were analyzed by Lung Cancer Panel 45 Genes and Targeted RNAscan Panel on NGS, respectively. Variants from NGS with coverage of higher than 1000X, cutoff ≥3% alternate variant frequency were considered positive. The cutoff was validated by Real-time PCR. Clinical data correlation was analyzed. Thirty-one patients (39%) had stage I-II and 48 patients (61%) had stage III-IV disease. Mean age was 62.5 years old. Fifty-one patients (65%) were female and 55 patients (70%) were never-smoker. A majority of the patients (83.6%) were negative-PD-L1. All of the 13 PD-L1 positive patients were in stage III-IV, suggesting the increased likelihood of PD-L1 expression in advanced disease (p = 0.014). No difference in age, sex, smoking status, histological subtypes, and mutational status were seen between PD-L1 positive and negative group.However, PD-L1 negative was associated with a trend toward better survival (Table1). Subgroup analysis in stage IV patients with common EGFR mutations revealed PD-L1 positive status as a significant negative prognostic factor with HR of 3.00 (95% CI: 1.17, 7.73; P-value=0.023), whereas positive-PD-L1 patients with the other mutations showed a trend of worse survival outcome.Table 1Cox regression analysis of prognostic factors associated with overall survival of NSCLC patientsPrognostic factorsFollow up time (100 person-month)DeathMedian survival (mo)Univariate analysisMultivariate analysisNo.Rate (95% CI)HR (95% CI)p-valueAdjusted HR (95% CI)p-valueAge1.00 (0.98, 1.03)0.893-Sex0.250Male8.71182.07 (1.30, 3.28)22.81.43 (0.79, 2.59)0.243-Female21.14281.32 (0.91, 1.92)53.91-PDL10.002Negative (<1%)28.05351.25 (0.90, 1.74)53.911Positive (≥1%)1.80116.09 (3.38, 11.00)7.13.52 (1.73, 7.16)0.0011.88 (0.83, 4.22)0.128Stage<0.001I-II19.2060.31 (0.14, 0.70)NR11III-IV10.65403.76 (2.75, 5.12)20.111.09 (4.26, 28.87)<0.00110.03 (3.67, 27.41)<0.001Smoking status0.011Never smoker24.04281.16 (0.80, 1.69)76.211Ex-smoker4.55102.20 (1.18, 4.09)20.11.70 (0.82, 3.52)0.1541.02 (0.47, 2.23)0.962Current smoker1.2686.33 (3.17, 12.66)8.73.76 (1.68, 8.41)0.0011.70 (0.74, 3.88)0.208EGFR0.825Mutation22.99351.52 (1.09, 2.12)31.90.93 (0.47, 1.83)0.824-No mutation6.87111.60 (0.89, 2.89)33.51-ALK0.869Positive2.2831.32 (0.43, 4.09)NR1.11 (0.33, 3.78)0.867-Negative16.50191.15 (0.73, 1.81)76.21-KRAS0.051Mutation13.12120.91 (0.52, 1.61)NR0.53 (0.27, 1.03)0.062-No mutation16.73342.03 (1.45, 2.84)31.11-Number of co-MT0.045< 100011.84272.28 (1.56, 3.33)22.811≥ 100018.02191.05 (0.67, 1.65)57.60.55 (0.30, 0.99)0.0471.22 (0.61, 2.41)0.574 Open table in a new tab Positive-PD-L1 is significantly associated with advanced disease and a trend toward unfavorable prognosis. The detrimental effect of PD-L1 is significant in stage IV patients with common EGFR mutations. A confirmatory study with a larger sample size would better identify the prognostic benefit of PD-L1 status in vast subsets.