Effect of concurrent TP53 mutation in EGFR/ALK/ROS1 positive non-small cell lung cancer treated with first-line TKI therapy: A Single Institution Retrospective Study.

Abstract

e20592 Background: Tyrosine Kinase Inhibitors (TKI) are the mainstay of therapy for patients (pts) with EGFR/ALK/ROS1 positive (pos) non-small cell lung cancer (NSCLC), however resistance to these drugs is inevitable and remains a clinical challenge. The cause for early resistance leading to progression has not been fully understood, but several mechanisms have been reported. We conducted a retrospective study to determine the impact of concurrent TP53 mutation (TP53m) in this population. Methods: NSCLC pts treated with first line TKI from 01/2014 to 06/2017 were studied. Descriptive statistics were computed. Progression was equated with TKI resistance (TKIr). We compared time to TKIr among pts with TP53m to those without. Standard survival analysis methods (i.e., Kaplan-Meier curves and multivariable Cox proportional hazards regression) were used. Results: Forty-two subjects on first line treatment TKI were included. The mean (SD) age was 67.2 (14.7) years. 37 (88%) were EGFR, 4 (10%) were ALK and 1 (2%) were ROS pos. 76% were female, 50% White, 74% non-smokers and 50% had a TP53m. The estimated median time to TKIr was 19.4 months. At 24 months from start of therapy, the predicted probability of not reaching TKIr was 46% (95% CI: 26-64%). The estimated median time to TKIr among those without TP53m is 19.4 months vs 14.4 months in those with TP53m (p = 0.13). The predicted probability of no TKIr at 12 months from start of therapy among those with and without TP53m were 59% and 80%, respectively. In multivariable analysis, TP53 status remained nonsignificant (p = 0.08) after adjusting for line of therapy. Conclusions: TP53m has been associated with worse prognosis in various cancers. The results from the studies looking at association between TP53m and NSCLC with targetable mutation have been mixed, with few studies demonstrating the association of TP53m with poor survival and earlier treatment resistance. In our study, although there was a tendency towards improved survival and delayed TKIr in the cohort without TP53m, it was not statistically significant, which may be due to small sample size. Further studies looking at concurrent TP53m and targetable mutation are required, which may help clinicians deciding how to direct therapy in this population.