Influence of <i>TP53</i> Mutation on Survival in Patients With Advanced <i>EGFR</i>-Mutant Non-Small-Cell Lung Cancer.

Abstract

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