The prognostic value of KRAS mutation subtypes and PD-L1 expression in patients with lung adenocarcinoma.

e20022 Background: KRAS gene mutations are found in 20-30% of non-small cell lung cancer (NSCLC), especially in adenocarcinoma. Compared to EGFR and ALK mutations, KRAS mutation in NSCLC may be associated with poorer prognosis. However, prognostic value of different KRAS mutation subtypes in NSCLC remains unknown. The goal of this study is to evaluate the association of KRAS mutation subtypes, PD-L1 expression and clinical outcome in patients diagnosed with primary lung adenocarcinoma. Methods: A total of 256 patients diagnosed with KRAS mutated (determined by pyrosequencing) lung adenocarcinoma between 2011 and 2015 in AdventHealth-Orlando were evaluated for their cancer staging, Relapse-free survival (RFS) and overall survival (OS). PD-L1 staining was performed in a subgroup of 95 patients from the same cohort. PD-L1 expression was determined with immunohistochemistry staining using Ventana PD-L1 (SP263) assay. Results: In this cohort of patients, 65 had stage I disease, 29 stage II, 49 stage III, 110 stage IV and 3 with no clinical stage information; 104 male, 152 female; median age 67. All patients received standard surgical/chemo/radio therapy according to the disease stages. Only one single patient received immunotherapy. Nine subtypes of KRAS mutation were detected, predominantly in codon 12. Three major subtypes account for 83.6% KRAS mutations, namely G12C (45.7%), G12V (21.9%) and G12D (16.0%). We found that these three major subtypes had no difference in cancer stages (P = 0.58) or brain metastasis at diagnosis (P = 0.78). Kaplan Meier analysis also showed similar OS and RFS among all KRAS subtype. 34% of KRAS mutated patients were found to be PD-L1 positive with tumor proportion score of greater than or equal to 1. PD-L1 expression status was indistinct among the three major mutation subtypes (P = 0.38). Of interest, among patients with G12C mutation, positive PD-L1 expression was associated with significantly shorter OS (5.7 vs 12.8 months; P = 0.007). In contrast, for patients with other KRAS mutation subtypes, PD-L1 expression status had no impact on OS (P = 0.63). Conclusions: The clinical courses, including tumor stage at diagnosis, presence of brain metastasis, OS and RFS, are similar among lung adenocarcinoma patients with different KRAS mutation subtypes. Additionally, PD-L1 expression status appears to be independent of KRAS mutation subtypes. Of note, concurrent PD-L1 expression and G12C mutation is associated with particularly poorer prognosis. Further study is needed to see if PD1/PD-L1 block may improve outcome of this group of patients.