PD-L1 score as a prognostic biomarker in asian early-stage epidermal growth factor receptor-mutated lung cancer.

Aim: To determine the prognostic value of programmed death-ligand 1 (PD-L1) score in early-stage epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC), contrasted against EGFR-wildtype NSCLC.
Methods: Consecutive patients with Stage IA-IIIA NSCLC diagnosed 1st January 2010-31st December 2019 at National Cancer Centre Singapore with evaluable EGFR and PD-L1 status were included. Co-primary end-points were 2-year disease-free survival (DFS) and 5-year overall survival (OS) by Kaplan-Meier method.
Results: 455 patients were included (267 EGFR-mutated, EGFR-M+; 188 EGFR-wildtype, wt). Median age at diagnosis was 65 years, 52.3% (238/455) of patients were males, 62.9% (286/455) of patients were never-smokers and 92.5% (421/455) of patients had R0 resection. Stage IA comprised 42.4% (193/455) of patients, Stage IB comprised 23.1% (105/455) of patients, Stage IIA comprised 10.8% of patients (49/455), Stage IIB comprised 5.1% of patients (23/455) and Stage IIIA comprised 18.7% (85/455) of patients. Among EGFR-M+, 45.3% (121/267) were Ex19del and 41.9% (112/267) were L858R. PD-L1 ≥1% among EGFR-M+ and EGFR-wt was 45.3% (121/267) and 54.8% (103/188) respectively (p = 0.047). At median follow-up of 47 months, 178 patients had relapsed. Among EGFR-M+, 2-year DFS comparing PD-L1 <1% and PD-L1 ≥1% was 78.1% and 67.6% (p = 0.007) while 5-year OS was 59.5% and 42.8% (p = 0.001), respectively. Controlling for age, gender, lymphovascular invasion, adjuvant therapy and resection margin status, PD-L1 ≥1% (hazard ratio, HR 2.18, 95% CI 1.04-4.54, p = 0.038), stage IIB (HR 7.78, 95% CI 1.72-35.27, p = 0.008) and stage IIIA (HR 4.45, 95% CI 1.44-13.80, p = 0.01) emerged as independent predictors of inferior OS on multivariable analysis. In exploratory analysis, genomic analysis of 81 EGFR-M+ tumours was performed. PD-L1 ≥1% tumours had significantly higher rates of TP53 mutations (36.1% versus 15.6%, p = 0.04), with predominantly missense mutations.
Conclusion: PD-L1 ≥1% is an independent predictor of worse OS among early-stage EGFR-mutated NSCLC and is associated with inferior DFS regardless of EGFR status. PD-L1 score as a risk stratification factor should be evaluated in prospective adjuvant studies among EGFR-mutated NSCLC.
Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Saw reported receiving personal fees from Pfizer, Bayer, AstraZeneca and MSD outside the submitted work. Dr A. Tan reported receiving personal fees from Amgen and Pfizer outside the submitted work. Dr Lai reported receiving personal fees from Amgen and grants from Merck, Astra Zeneca, Pfizer, Bristol Myers Squibb, and Roche outside the submitted work. Dr D.W.T. Lim reported receiving grants from Bristol Myers Squibb and Boehringer-Ingelheim and personal fees from Merck, Roche, Pfizer, Taiho, and Astra-Zeneca outside the submitted work. Dr Kanesvaran reported receiving personal fees from Merck, Bristol Myers Squibb, Astellas, Johnson & Johnson, Eisai, Ipsen and Novartis outside the submitted work. Dr Ng reported serving on advisory boards for Boehringer Ingelheim and Merck outside the submitted work. Dr W.L. Tan reported receiving personal fees from Amgen, Merck and Novartis outside the submitted work. Dr. Ong reported receiving personal fees from AstraZeneca, MSD and Medtronic, non-financial support from Johnson & Johnson, personal fees and non-financial support from Stryker outside the submitted work. Dr D.S.W. Tan reported grants from AstraZeneca and Amgen and personal fees from Novartis, Boehringer Ingelheim, Bayer, GlaxoSmithKline, Janssen, Amgen, and C4 Therapeutics outside the submitted work. No other disclosures were reported.
(Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)