Prognostic value of KRAS mutations, TP53 mutations and PD-L1 expression among lung adenocarcinomas treated with immunotherapy

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 of KRAS and/or TP53 mutations 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 a KRAS mutation, predominantly together with mutations in TP53 (41%) or STK11 (10%). Higher expression of PD-L1 was seen among patients with KRAS mutations (p=0.002) and EGFR wild 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 to KRAS mutation status, TP53 mutation status or PD-L1 expression. The HR for concomitant mutations in TP53 and KRAS was 0.78 (95% CI 0.62 to 0.99) for OS and 0.43 (0.21 to 0.88) for PFS. Furthermore, concomitant TP53 and KRAS mutations predicted a better PFS (p=0.015) and OS (p=0.029) compared with no mutations or a single mutation in either TP53 or KRAS. ConclusionMutations in TP53 together with KRAS may serve as a potential biomarker for survival benefits with immunotherapy.

Automated summary

This study investigates the association between oncogenic alterations and PD-L1 expression in lung adenocarcinomas, as well as the prognostic value of KRAS and/or TP53 mutations in patients treated with immunotherapy. The results suggest that KRAS mutations and higher expression of PD-L1 are associated. Additionally, concomitant TP53 and KRAS mutations may serve as a potential biomarker for improved survival with immunotherapy.