The effect of PIK3CA gene mutations on the prognosis of patients with advanced non-small cell lung cancer
QIAO Jianbing
LU Ju
QUAN Lin
XIA Chunwei
Abstract：Objective To investigate the mutation status of phosphatidylinositol 3-kinase catalytic subunit alpha(PIK3CA)in advanced non-small cell lung cancer(NSCLC)and its impact on the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs)and patient prognosis.Methods Clinical data of 64 patients with PIK3CA-mutant advanced NSCLC diagnosed at the Affiliated Brain Hospital of Nanjing Medical University from January 2016 to March 2023 were collected.The association between different mutation sites and clinicopathological characteristics as well as prognosis was analyzed.Furthermore,39 patients with coexisting EGFR and PIK3CA mutations were compared with 84 patients harboring EGFR mutations alone to evaluate the influence of PIK3CA mutations on EGFR-TKI efficacy and prognosis.Univariate and multivariate Cox regression models were used to identify factors associated with prognosis.Results The most frequent PIK3CA mutation sites were E545K(20/64),H1047R(16/64),and E542K(12/64).The most common co-mutations were EGFR(29/64)and TP53(13/64).There were no significant differences in objective response rate(ORR:36.1％vs.28.6％),disease control rate(DCR:61.1％vs.61.9％),1-year survival rate(58.3％vs.57.1％),2-year survival rate(25.0％vs.23.8％),median progression-free survival(PFS:6.9 months vs.5.8 months),or median overall survival(OS:15.4 months vs.14.2 months)between the PIK3CA Exon 9 and Exon 20 mutation groups(all P＞0.05).Compared with the EGFR mutation group,The EGFR and PIK3CA co-mutant group had worse clinical efficacy,including lower ORR(41.0％vs.60.7％)and DCR(76.9％vs.95.2％),reduced 1-year survival rate(71.8％vs.94.0％)and 2-year survival rate(38.5％vs.67.9％),as well as shorter median PFS(7.9 months vs.14.2 months)and median OS(18.8 months vs.28.0 months),and the difference was statistically significant(all P＜0.05).Multivariate analysis identified PIK3CA mutation(HR=2.364,95％CI:1.578-3.542)and ECOG performance status(HR=2.319,95％CI:1.550-3.468)were independent risk factors for OS in EGFR mutation patients(P＜0.05).Conclusion The differential mutation of Exon 9 and Exon 20 of PIK3CA gene had no effect on short-term efficacy and prognosis of patients.The co-mutation of EGFR and PIK3CA affects the therapeutic effect of EGFR-TKI,increases the risk of patient death,and is an independent risk factor for poor prognosis of patients with targeted therapy.
Keywords：non-small cell lung cancerepidermal growth factor receptor mutationphosphatidylinositol 3-kinase catalytic subunit alpha mutationtargeted therapyprognosis
Publication Date：2026-02-28
Online Publishing Date：2026-04-01(First online date of this platform, not the publication date of the document)
Pages：6( 161-166 )