Abstract
PURPOSE: TP53 mutation (MT) in epidermal growth factor receptor (EGFR) -MT non-small cell lung cancer (NSCLC) is associated with poor response to targeted therapy; however, its impact on survival is not clearly established. PATIENTS AND METHODS: We performed an analysis of patients with stage IV EGFR MT NSCLC with available gene sequencing data. Associations between baseline characteristics; molecular profile, including TP53 MT; and survival outcomes were assessed. RESULTS: We identified 131 consecutive patients with EGFR MT; 81 (62%) had a TP53 MT, and 55 (42%) had other coexisting oncogenic MTs. Emergent EGFR T790M MT was observed in 42 patients (32%). Overall survival (OS) was longer for younger patients (P = .003), never smokers (P = .002), those with Eastern Cooperative Oncology Group performance status 0 to 1 (P = .004), and emergent T790M MT (P = .018). TP53 MT (P = .021) and other coexisting oncogenic MTs (P = 0.011) were associated with inferior OS. In a multivariable regression analysis adjusted for age, smoking, Eastern Cooperative Oncology Group performance status, and the presence of TP53 MT (P = .063) and other coexisting MTs (P = .064) did not achieve statistical significance. Patients with EGFR T790M/TP53 double MT had worse OS compared with patients with T790M MT alone (46.4 months v 82.9 months). In our series, five patients transformed to small-cell lung cancer (5.6%). All had TP53 MT. In four patients, allelic fraction of TP53 MT increased at the time of transformation. CONCLUSION: The presence of TP53 and other coexisting MTs in EGFR MT NSCLC were associated with inferior OS, including patients with emergent T790M MT. An increase in TP53 mutation allelic fraction may potentially be a useful clinical predictor of small-cell transformation.