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.
Identify all potential conflicts of interest that might be relevant to your comment.
Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.
Err on the side of full disclosure.
If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response.
Not all submitted comments are published. Please see our commenting policy for details.
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
Coronavirus Resource Center
Customize your JAMA Network experience by selecting one or more topics from the list below.
Create a personal account or sign in to: