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

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.

Impact of gender and mutational differences in hormone receptor expressing non-small cell lung cancer

“…However, EGFR and TP53 co-mutations were seen at a similar prevalence in HR+ and HR- NSCLC, but they were more prevalent in females in our HR+ NSCLC population. TP53 co-mutation with EGFR has conferred worse overall survival to first line EGFR TKI use in real world settings and our gender disparity findings in HR+ NSCLC suggest that further investigation is needed ( 43 ).…”

The role of oncogenes and tumor suppressor genes in determining survival rates of lung cancer patients in the population of North Sumatra, Indonesia

“…Seeing most of the studies in various parts of the world related to this shows that TP53 mutation is an important marker of poor prognosis and predictor of lung cancer, especially in cases of NSCLC with EGFR mutations. [50][51][52][53][54] By comparing TP53 mutation group with TP53 wild-type group, a recent meta-analysis on this issue confirmed worse OS of TP53 in EGFR mutant lung cancers by 1.7 times in comparison to wild-type group (hazard ratio 1.73, 95% CI 1.22-2.44, P=0.002). 54 Patients with TP53 mutation on exon 5, exon 7, exon 8 and exon 9 demonstrated better prognosis than exon 4, exon 6, mutation of unknown site and multiple mutated patients.…”

“…TP53 wild type patients demonstrated the best prognosis, good mutated patients demonstrated middle prognosis and poor mutated patients demonstrated the worst prognosis in EGFR mutations. 51,52,54 Regarding the management of lung cancer patients with different type of mutations in the sample of this study, each sample has received personalized treatment and indeed not all lung cancer patients receive tyrosine kinase inhibitor (TKI) drugs. The management of lung cancer patients in the sample is quite diverse covering every aspect from surgery, chemotherapy, to targeted therapy.…”

“…TP53 wild type patients demonstrated the best prognosis, good mutated patients demonstrated middle prognosis and poor mutated patients demonstrated the worst prognosis in EGFR mutations. 51 , 52 , 54 …”