There is an urgent need to identify new predictive biomarkers for treatment response to both platinum doublet chemotherapy (PT) and immune checkpoint blockade (ICB). Here, we evaluated whether treatment outcome could be affected by KRAS mutational status in patients with metastatic (Stage IV) non-small cell lung cancer (NSCLC). All consecutive patients molecularly assessed and diagnosed between 2016–2018 with Stage IV NSCLC in the region of West Sweden were included in this multi-center retrospective study. The primary study outcome was overall survival (OS). Out of 580 Stage IV NSCLC patients, 35.5% harbored an activating mutation in the KRAS gene (KRASMUT). Compared to KRAS wild-type (KRASWT), KRASMUT was a negative factor for OS (p = 0.014). On multivariate analysis, KRASMUT persisted as a negative factor for OS (HR 1.478, 95% CI 1.207–1.709, p < 0.001). When treated with first-line platinum doublet (n = 195), KRASMUT was a negative factor for survival (p = 0.018), with median OS of 9 months vs. KRASWT at 11 months. On multivariate analysis, KRASMUT persisted as a negative factor for OS (HR 1.564, 95% CI 1.124–2.177, p = 0.008). KRASMUT patients with high PD-L1 expression (PD-L1high) had better OS than PD-L1highKRASWT patients (p = 0.036). In response to first-line ICB, KRASMUT patients had a significantly (p = 0.006) better outcome than KRASWT patients, with a median OS of 23 vs. 6 months. On multivariable Cox analysis, KRASMUT status was an independent prognostic factor for better OS (HR 0.349, 95% CI 0.148–0.822, p = 0.016). kRAS mutations are associated with better response to treatment with immune checkpoint blockade and worse response to platinum doublet chemotherapy as well as shorter general OS in Stage IV NSCLC.
BackgroundPembrolizumab, a humanized antibody targeting Programmed Cell Death 1 (PD-1), is used as first-line therapy for patients with metastatic Non-Small Cell Lung Cancer (NSCLC) expressing Programmed Death Ligand 1 (PD-L1). However, not all PD-L1 expressing patients respond to pembrolizumab. Thus, there is an urgent need to identify new predictive biomarkers for response to immune checkpoint blockade (ICB) therapy. KRAS mutational status has been suggested to affect treatment outcome, but no clear consensus could be drawn for previous studies.MethodsAll consecutive patients diagnosed between 2016-2018 with metastatic NSCLC (stage IV) in the region of West Sweden with molecular characterization available were included in this multi-centers retrospective study. Primary study outcome was overall survival (OS). Baseline patients’ characteristics, histology type, mutational status, PD-L1 expression and first-line treatment were collected from patient charts and the Swedish Lung Cancer registry.ResultsOut of 580 stage IV NSCLC patients, 35.5% harbored a mutation in the KRAS gene (KRASMUT). Compared to KRAS wild-type (KRASWT), KRASMUT was a negative factor for OS (p = 0.014). On multivariate analysis, KRASMUT persisted as a negative factor for OS (HR 1.288, 95% CI 1.091-1.521, p = 0.003). When treated with first-line platinum doublet, KRASMUT (n = 219) is a significant (p = 0.001) negative factor for survival with median OS 9 months vs KRASWT 14 months. Patients on KRAS mutational status and PD-L1 expression levels had a significant better OS in KRASMUT with increased PD-L1 expression (p = 0.036) but not for KRASWT. On first-line ICB, KRASMUT had a significant (p = 0.006) better outcome than KRASWT with a median OS 23 vs 6 months. On multivariable Cox analysis, KRASMUT status and Performance Status (PS) 0-1 were independent prognostic factors for better OS (HR 0.349, 95%CI 0.148-0.822, p = 0.016 and HR 0.398, 95 % CI 0.165-0.963, p =0.041).ConclusionsKRAS mutations combined with PD-L1high is a better predictive marker for response to first-line monotherapy with pembrolizumab than only PD-L1high in patients with metastatic NSCLC.
Purpose: The aim of this study it to investigate the combined impact of KRAS mutational status and tumor size on overall survival and risk of death in stage I and II NSCLC. Methods: All consecutive patients molecularly assessed and diagnosed between 2016-2018 with stage I-II NSCLC in the region of West Sweden were included in this multi-center retrospective study. Primary study outcome was overall survival (OS) and risk of death (HR). Results: Out of 310 Stage I-II NSCLC patients, 37% harbored an activating mutation in the KRAS gene (KRASMUT). Our study confirmed staging and tumor size as prognostic factors. KRAS mutational status was not found to impact overall survival and no difference in risk of death was observed when combining KRAS mutational status and primary tumor size. Conclusions: KRAS mutations in combination with primary tumor size are not associated with a worse prognosis in stage I and II NSCLC.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.