For patients with advanced non–small-cell lung cancer (NSCLC) without a driver alteration and programmed cell death ligand 1 (PD-L1) expression of 50% or greater, immune checkpoint inhibition (ICI) monotherapy or in combination with chemotherapy is standard first-line therapy. When deciding between these options, clinicians consider disease burden and comorbidities; however, to our knowledge, no biomarkers have been shown to predict differential benefit or harm.
KRAS variants in NSCLC are associated with smoking history, higher PD-L1 expression, and responsiveness to ICI monotherapy.1-3 The KEYNOTE-042 study demonstrated an overall survival (OS) benefit for first-line pembrolizumab over chemotherapy in patients with PD-L1 expression of 1% or greater.4 In an exploratory analysis, this benefit was seen regardless of KRAS status, but was more pronounced in patients with KRAS variants (median OS [mOS], 28 vs 11 months; hazard ratio [HR], 0.42;, 95% CI, 0.22-0.81) than those without KRAS variants (mOS, 15 vs 12 months; HR, 0.86; 95% CI, 0.63-1.18).1 However, to our knowledge, no prior studies have evaluated the association of KRAS status with outcomes following ICI monotherapy vs chemoimmunotherapy in patients with PD-L1 of 50% or greater.
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Sun L, Hsu M, Cohen RB, Langer CJ, Mamtani R, Aggarwal C. Association Between KRAS Variant Status and Outcomes With First-line Immune Checkpoint Inhibitor–Based Therapy in Patients With Advanced Non–Small-Cell Lung Cancer. JAMA Oncol. 2021;7(6):937–939. doi:10.1001/jamaoncol.2021.0546
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