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

SIMPLE SUMMARY: There is conflicting evidence on the impact of TP53 co-mutations on survival in patients with EGFR-mutated advanced non-small cell lung cancer (aNSCLC). This observational study used data from a de-identified database to assess the role of TP53 co-mutation on survival in patients with EGFR-mutated aNSCLC (n = 356). We observed a significant decrease in survival outcomes (namely real-world progression-free survival [rwPFS] and overall survival [OS]) duration in the group of aNSCLC patients with presence of TP53 co-mutation compared to those with wild-type TP53 tumors. TP53 co-mutations were also associated with worse outcomes by subgroups, including type of EGFR-mutation and first-line treatment. Together, these findings indicated negative impact of TP53 co-mutation in outcomes for patients with EGFR-mutated aNSCLC. ABSTRACT: TP53 co-mutations have shown association with poor prognosis in various solid tumors. For EGFR-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 EGFR-mutated aNSCLC between January 2014 and December 2020 were identified. Clinical outcomes were evaluated by TP53-mutational status. In 356 eligible EGFR-mutated aNSCLC patients (median age 68 years), 210 (59.0%) had TP53 co-mutation and 146 (41.0%) had TP53 wild-type tumor. Unadjusted analysis showed significantly shorter survival in patients with TP53 co-mutation versus TP53 wild-type (rw progression-free survival [rwPFS]: HR = 1.4, 95% CI 1.1–1.9, p = 0.0196; overall survival [OS]: HR = 1.6, 95% CI 1.1–2.2, p = 0.0088). Multivariable analysis confirmed independent association between TP53 co-mutation and worse rwPFS (HR = 1.4, 95% CI 1.0–0.9, p = 0.0280) and OS (HR = 1.4, 95% CI 1.0–2.0, p = 0.0345). Directionally consistent findings were observed for response rates, and subgroups by EGFR-activating mutation and first-line (1 L) therapy, with more pronounced negative effect in 1 L EGFR-TKI subgroup. TP53 co-mutations negatively affected survival in patients with EGFR-mutated aNSCLC receiving standard 1 L therapy in real-world practice.