Prognostic Value Of TP53 Mutation In Patients With Advanced Non-small Cell Lung Cancer With EGFR Mutation

Background Previous studies have shown that concomitant genetic alterations is related to the primary resistance of epidermal growth factor receptor(EGFR)tyrosine kinase inhibitor(TKIs)in patients with EGFR mutant advanced non-small cell lung cancer(NSCLC).However,the prognostic value of TP53 co-mutation in this population is still controversial.Methods A retrospective study was conducted to screen patients with advanced NSCLC with EGFR mutation from February 2017 to December 2019 in the Guangxi Tumor Hospital.All patients completed the Next-generation gene sequencing(NGS)at the initial diagnosis to determine the status of EGFR and TP53 genes.The correlation between the TP53 gene status,baseline clinical characteristics and treatment effect was statistically analyzed.The primary end point was progression-free survival(PFS),and the secondary end points were objective response rate(ORR)and overall survival(OS).Results Among 78 patients with advanced NSCLC with EGFR mutation,the incidence of TP53 mutation was 69.23%(54/78),with a median age of 59.9years(range 41-85 years),33 males(42.3%)and 45 females(57.7%),75 cases of adenocarcinoma(96.2%).In the subgroup analysis of 49 patients with EGFR mutant advanced NSCLC who received EGFR-TKIs single drug on first-line treatment(30 TP53 mutant,19 TP53 wild type),TP53 co-mutation group showed shorter median PFS(9.07 months vs 14 months,HR2.8,95%CI 1.3-6.0,P=0.005)and shorter median OS(19.53 months vs not reached,HR3.8,95%CI1.1-13.1,P=0.032),but we did not observe a significant difference in ORR between the two groups(52.50% vs 63.16%,P>0.05).After multivariate analysis,we confirmed that TP53 mutation is an independent adverse prognostic factor in patients with EGFR mutant advanced NSCLC.For the advanced NSCLC patients with TP53/EGFR co-mutation,the first-line treatment strategy of EGFR-TKIs combined with Platinum-based chemotherapy significantly improved ORR(64.30% vs 52.50%,P = 0.0165)compared with EGFR-TKIs single drug treatment,and prolonged PFS(14.67 months vs 9.07 months,HR0.3,95% CI 0.1-0.8,P=0.012)and OS(27.57 months vs 20.37 months,HR0.1,95%CI 0.0-1.0,P=0.019)than EGFR-TKIs monotherapy.Conclusion TP53 mutation is an independent adverse prognostic factor in patients with EGFR mutant advanced NSCLC.For patients with advanced NSCLC with TP53 / EGFR co-mutation,EGFR-TKIs combined with Platinum-based chemotherapy can reduce the risk of progression and death compared with EGFR-TKIs monotherapy.