Prognostic value ofKRASmutations,TP53mutations and PD-L1 expression among lung adenocarcinomas treated with immunotherapy

Abstract

AimsThe aim of this study was to investigate the association between oncogenic alterations and programmed cell death ligand 1 (PD-L1) expression in lung adenocarcinomas, as well as the prognostic value ofKRASand/orTP53mutations in patients treated with immunotherapy.MethodsThis study is a retrospective cohort study of 519 patients with lung adenocarcinomas analysed for mutations and PD-L1 expression. Data were collected from electronic pathology record system, next-generation sequencing system, and clinical databases. Association between mutations and PD-L1 expression was investigated, as well as survival statistics of the 65 patients treated with immunotherapy.Results41% of the samples contained aKRASmutation, predominantly together with mutations inTP53(41%) orSTK11(10%). Higher expression of PD-L1 was seen among patients withKRASmutations (p=0.002) andEGFRwild type (p=0.006). For patients treated with immunotherapy, there was no statistically significant difference for overall survival (OS) and progression-free survival (PFS) according toKRASmutation status,TP53mutation status or PD-L1 expression. The HR for concomitant mutations inTP53andKRASwas 0.78 (95% CI 0.62 to 0.99) for OS and 0.43 (0.21 to 0.88) for PFS. Furthermore, concomitantTP53andKRASmutations predicted a better PFS (p=0.015) and OS (p=0.029) compared with no mutations or a single mutation in eitherTP53orKRAS.ConclusionMutations inTP53together withKRASmay serve as a potential biomarker for survival benefits with immunotherapy.