Impact of <i>KRAS</i> and <i>TP53</i> Co-Mutations on Outcomes After First-Line Systemic Therapy Among Patients With <i>STK11</i>-Mutated Advanced Non-Small-Cell Lung Cancer.
retrospective_cohort · Level III
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- Also identified by DOI 10.1200/PO.18.00326 and PMC identifier 6699781.
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Abstract
The <i>STK11</i> gene encodes a serine/threonine protein kinase that regulates cell polarity and functions as a tumor suppressor. Patients with non-small-cell lung cancer (NSCLC) and <i>STK11</i> mutations often have other co-mutations. We evaluated the impact of <i>KRAS</i> and <i>TP53</i> co-mutations on outcomes after first-line systemic therapy for patients with metastatic or recurrent NSCLC that harbors <i>STK11</i> mutations. We conducted a retrospective review of patients with metastatic NSCLC and <i>STK11</i> mutations treated at the University of Pennsylvania. <i>STK11</i> mutations were identified through next-generation sequencing (NGS) in tissue or plasma. Cox proportional hazard models were used to determine the relationship between <i>STK11</i> co-mutations and survival outcomes. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). From February 2013 to December 2016, samples from 1,385 patients with NSCLC were analyzed by NGS; of these, 77 patients (6%) harbored an <i>STK11</i> mutation (n = 56, tissue; n = 21, plasma). Of the 62 patients included, 18 had an <i>STK11</i> mutation alone, 19 had <i>STK11/KRAS,</i> 18 had <i>STK11/TP53,</i> and seven had <i>STK11/KRAS/TP53.</i> Patients with <i>STK11/KRAS</i> co-mutations had a worse median PFS (2.4 months) compared with <i>STK11</i> alone (5.1 months; log-rank <i>P</i> = .048), <i>STK11/TP53</i> (4.3 months; log-rank <i>P</i> = .043), and <i>STK11/KRAS/ TP53</i> (13 months; log-rank <i>P</i> = .03). Patients with <i>STK11/KRAS</i> co-mutation experienced shorter median OS (7.1 months) compared with <i>STK11</i> alone (16.1 months; log-rank <i>P <</i> .001), <i>STK11/TP53</i> (28.3 months; log-rank <i>P</i> < .001), and <i>STK11/KRAS/TP53</i> (22 months; log-rank <i>P</i> = .025). Among patients with advanced NSCLC and <i>STK11</i> mutations treated with first-line systemic therapy, co-mutation with <i>KRAS</i> was associated with significantly worse PFS and OS. By contrast, co-mutation of <i>STK11</i> with <i>TP53</i> conferred a better prognosis.