Efficacy And Safety Analyses Of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors Combined With Chemotherapy In Advanced Non–small-cell Lung Cancer With An EGFR/TP53 Co-mutation

Objective:This retrospective study intends to analyze the efficacy and safety of epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs)combined with chemotherapy in the first line treatment of advanced non-small lung cancer(NSCLC)patients with an EGFR/TP53 co-mutation.Methods:Clinical data of 301 advanced NSCLC patients treated in the First Affiliated Hospital of Nanchang University from January 1,2016 to October 31,2020 were collected.All the patients were confirmed with an EGFR/TP53 co-mutation using next-generation sequencing(NGS)simultaneously.Patients who met the criteria were divided into EGFR-TKIs monotherapy group(n=61)and EGFR-TKIs combined with chemotherapy group(n=34).Therapeutic efficacy including objective response rate(ORR)and disease control rate(DCR)were evaluated in accordance with the Response Evaluation Criteria in Solid Tumors 1.1(RECIST1.1),and Adverse event(AE)was evaluated according to Common Terminology Criteria for Adverse Events5.0(CTCAE5.0).Progression free survival(PFS)and overall survival(OS)were calculated using the Kaplan-Meier method,and log-rank test was used for comparison between groups.Independent indicators associated with PFS and OS were calculated using univariate and multivariate cox regression models.Result:1.The ORR was significantly improved in combination group versus monotherapy group(55.9% vs 34.4%,p = 0.042).But there were no statistically significant differences between combination group and monotherapy group in DCR(97.1% vs 91.8%,p = 0.313).2.The median PFS of the monotherapy group and combination group were 11.1months and 16.1 months respectively(p = 0.001).While the median OS of the monotherapy group and combination group were 28.2 months and 36.9 months(p =0.081).When patients with brain metastases were excluded,the median PFS of the combination group was longer than the monotherapy group(18.2 vs.11.6 months,p=0.001).OS differences between the combination group and the monotherapy group were also statistically significant(48.4 vs.28.8 months,p = 0.001).3.Both univariate and multivariate analysis showed that brain metastasis and treatment methods were independent factors affecting disease progression of advanced NSCLC patients with an EGFR/TP53 co-mutation(p<0.05).Clinical stage,brain metastases,EGFR21 L858 R mutation,and T790 M mutation status at first progression were independent prognostic factors for overall survival(p<0.05).4.Adverse events of all grades related to treatment in the monotherapy group and combination group have no significant difference(59.0% vs.70.6%,p=0.262),but adverse events such as myelosuppression,liver dysfunction,vomiting and constipation occurred more frequently in the combination group(p<0.05).The rate of grade ≥3 treatment-related adverse events in the combination group was significantly higher than that in the monotherapy group(32.4% vs.13.1%),and the difference was statistically significant(p=0.025).Conclusion:1.Our study indicates that EGFR-TKIs combined with chemotherapy could significantly improve ORR and PFS of advanced NSCLC patients with EGFR/TP53co-mutation compared with EGFR-TKIs monotherapy.2.For EGFR/TP53 co-mutation advanced NSCLC patients without brain metastases,EGFR-TKIs combined with chemotherapy in the first line treatment has better efficacy and controllable safety,which can be used as a reference for clinical treatment.