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

Abstract Objectives The prognostic value of different KRAS mutation subtypes and their association with PD-L1 expression in lung adenocarcinoma (LADC) remain unclear. We examined the association of KRAS mutation subtypes with clinical outcomes and PD-L1 expression status. Materials and Methods Patients diagnosed with K-RAS mutated LADC were evaluated for PD-L1 expression, cancer staging, overall survival (OS) and relapse-free survival (RFS). Results A cohort of 256 KRAS mutated LADC patients (median followed-up: 17 months) was studied. Three major subtypes of KRAS mutations were G12C (46.1%), G12V (21.7%) and G12D (15.7%). We found that all these subtypes had no impact on cancer stages, brain metastasis at diagnosis, OS and RFS. Among this cohort, 33% of 94 patients who had PD-L1 staining available were PD-L1 positive (≥ 1% of tumor cells). PD-L1 expression status was not significantly different among the three major mutation subtypes. Of interest, among patients with G12C mutation, positive PD-L1 expression was associated with significantly shorter OS (median survival: 5.7 vs 12.8 months, P=0.007). In multivariable analysis, PD-L1 positivity remained as an adverse factor for OS with hazard ratio of 4.44 (p = 0.0007). PD-L1 status did not impact OS in other subtypes of mutations. Conclusion KRAS mutation subtype is not associated with patient clinical outcomes or PD-L1 expression status. However, PD-L1 positivity appears negatively impacting OS in LADC patients with G12C mutation. Further study is needed to confirm our observation and to determine if PD1/PD-L1 antagonist may affect clinical outcome of patients with different KRAS mutation subtypes.