TP53 Co-Mutation Status Association with Clinical Outcomes in Patients with EGFR-Mutant Non-Small Cell Lung Cancer

Abstract

<i>TP53</i> co-mutations have shown association with poor prognosis in various solid tumors. For <i>EGFR</i>-mutated advanced non-small cell lung cancer (aNSCLC), conflicting results exist regarding its impact on survival. Clinical outcomes and genomic data were obtained retrospectively from the real-world (rw) de-identified clinicogenomic database. Patients who initiated therapy for <i>EGFR</i>-mutated aNSCLC between January 2014 and December 2020 were identified. Clinical outcomes were evaluated by <i>TP53</i>-mutational status. In 356 eligible <i>EGFR</i>-mutated aNSCLC patients (median age 68 years), 210 (59.0%) had <i>TP53</i> co-mutation and 146 (41.0%) had <i>TP53</i> wild-type tumor. Unadjusted analysis showed significantly shorter survival in patients with <i>TP53</i> co-mutation versus <i>TP53</i> wild-type (rw progression-free survival [rwPFS]: HR = 1.4, 95% CI 1.1-1.9, <i>p</i> = 0.0196; overall survival [OS]: HR = 1.6, 95% CI 1.1-2.2, <i>p</i> = 0.0088). Multivariable analysis confirmed independent association between <i>TP53</i> co-mutation and worse rwPFS (HR = 1.4, 95% CI 1.0-0.9, <i>p</i> = 0.0280) and OS (HR = 1.4, 95% CI 1.0-2.0, <i>p</i> = 0.0345). Directionally consistent findings were observed for response rates, and subgroups by <i>EGFR</i>-activating mutation and first-line (1 L) therapy, with more pronounced negative effect in 1 L <i>EGFR</i>-TKI subgroup. <i>TP53</i> co-mutations negatively affected survival in patients with <i>EGFR</i>-mutated aNSCLC receiving standard 1 L therapy in real-world practice.