Abstract 4212: PD-L1 expression, EGFR and KRAS mutations in unresectable stage III non-small cell lung cancer (NSCLC) patients

Abstract

Abstract Background: Anti-PD-L1 therapy may improve prognosis in advanced NSCLC. We examined the relation of PD-L1 expression, KRAS and EGFR mutations, with survival in unresectable stage III NSCLC patients. Methods: We obtained data on unresectable stage III NSCLC patients (defined via TNM AJCC staging and without surgery up to 120 days after diagnosis) diagnosed 2001-2012. We retrieved medical data from Danish population-based registries and paraffin-embedded tumor tissue from pathology archives. We assessed PD-L1 expression using the Ventana IHC (SP263) validated assay. We genotyped KRAS and EGFR using PCR-based kits. Follow-up began at NSCLC diagnosis and continued to death, emigration, or 31/12/2014. We used Cox regression to compute hazard ratios (HRs) and associated 95% confidence intervals (95%CI) for PD-L1, EGFR, and KRAS. Results: Among 305 patients, 183 (60%) were men, 167 (55%) were aged >65 years at diagnosis and none used immunotherapy; 148 (49%) had adenocarcinoma, 117 (38%) squamous histology, 96 (31.5%) had PD-L1 positive tumors (>=25%), 6 (2%) had EGFR mutations, and 69 (23%) had KRAS mutations. Among PD-L1 positive tumors, 55% had stage IIIA, 45% IIIB disease; 1% had EGFR and 34% had KRAS mutations. Among PD-L1 negative tumors, 54% had stage IIIA and 46% IIIB; 3% had EGFR and 16% had KRAS mutations. Median survival was similar in patients with KRAS wild-type and KRAS mutations (Hazards ratio (HR)=1.07; 95% CI=0.76-1.51). Patients with an EGFR mutation had a lower non-statistically significant risk of death (HR=0.75; 95% CI=0.28-2.06). Tumor cell positivity for PD-L1 (>=25% versus <25%) yielded an HR=0.80 (95%CI=0.60-1.07). Immune cell positivity for PD-L1 >=1% and >=25% yielded HRs of 0.50 (95%CI=0.39-0.66) and 0.45 (95%CI=0.30-0.67), respectively. Tumor infiltration by immune cells with PD-L1 measured as a continuous variable yielded an HR=0.96 (95%CI=0.93-0.99). Conclusion: Our findings suggest that PD-L1 expression and EGFR mutations, but not KRAS mutations, are associated with survival in this real-world Danish study of unresectable Stage III NSCLC patients. Citation Format: Deirdre Cronin-Fenton, Tapashi Dalvi, Elizabeth Hedgeman, Mette Norgaard, Lars Pedersen, Hanh Hansen, Jon Fryzek, Jill Walker, Anders Mellemgaard, Torben Rasmussen, Norah Shire, James Riggas, Danielle Potter, Stephen Hamilton-Dutoit, Henrik Sørensen. PD-L1 expression, EGFR and KRAS mutations in unresectable stage III non-small cell lung cancer (NSCLC) patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4212.