AUTHOR=Notario Lucía , Cucurull Marc , Cerdà Gabriela , Sanz Carolina , Carcereny Enric , Muñoz-Mármol Ana , Hernández Ainhoa , Domènech Marta , Morán Teresa , Sánchez-Céspedes Montse , Costa Marta , Mate Jose-Luis , Esteve Anna , Saigí Maria 

TITLE=Characterization of a cohort of metastatic lung cancer patients harboring KRAS mutations treated with immunotherapy: differences according to KRAS G12C vs. non-G12C

JOURNAL=Frontiers in Oncology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1239000

DOI=10.3389/fonc.2023.1239000

ISSN=2234-943X

ABSTRACT=<p>Approximately 20% of lung adenocarcinomas harbor activating mutations at <italic>KRAS</italic>, an oncogene with the ability to alter the tumor immune microenvironment. In this retrospective study, we examined 103 patients with <italic>KRAS</italic>-mutant lung adenocarcinoma who were treated with immunotherapy-based regimens and we evaluated the clinical outcomes according to PD-L1 expression and the type of <italic>KRAS</italic> mutation. Among all patients included, 47% carried <italic>KRAS G12C</italic> mutation whereas 53% harbored <italic>KRAS</italic> non-G12C mutations. PD-L1 status was available for 77% of cases, with higher expression among KRAS G12C tumors (p = 0.01). Better overall survival and progression-free survival were observed in high PD-L1 expression tumors, regardless of <italic>KRAS</italic> mutation type. The heterogeneous nature of KRAS-mutant tumors and the presence of other co-mutations may contribute to different outcomes to immunotherapy-based strategies.</p>