Predictive and prognostic potential of TP53 in patients with advanced non-small cell cancer treated with EGFR-TKI: Analysis of a phase III randomized clinical trial (CTONG 0901)

Abstract Background Mutations in TP53 are commonly found in patients with epidermal growth factor receptor (EGFR) mutant advanced non-small cell lung cancer (NSCLC). In this study, we determined the predictive and prognostic potential of different subtypes of TP53 using data from a phase III randomized trial (CTONG 0901). Patients and Methods The trial enrolled 195 patients who had undergone next-generation sequencing of 168 genes before treatment with EGFR tyrosine kinase inhibitors. Mutations in TP53 (exon 4 or 7, other mutations, and wild-type) were analyzed based on the therapeutic response and survival. A Cox proportional hazards model was used to determine the potential of the predictive and prognostic factors. Results All 195 patients harbored activating EGFR mutations: the most common concomitant mutations were TP53 (134/195, 68.7%), CTNNB1 (20/195, 10.3%), and RB1 (16/195, 8.2%). The genetic profiles between patient subgroups administered first-line (132, 67.7%) or later-line (63, 32.3%) treatments did not significantly differ. The median progression-free survival in patients with mutations in exon 4 or 7 of TP53, other TP53 mutations, and wild-type TP53 were 9.4, 11.0, and 14.5 months (P = 0.009), respectively. Overall survival times were 15.8, 20.0, and 26.1 months (P = 0.004), respectively. Mutations in exon 4 or 7 of TP53 served as independent prognostic factors for progression-free (P = 0.001) and overall survival (P = 0.004) in patients. Conclusion Mutations in exon 4 and/or 7 in TP53 are promising predictive and prognostic indicators in EGFR-mutated NSCLC.