The Efficacy Of Combined Regimens For Non-small Cell Lung Cancer Harboring EGFR Exon 21-L858R Mutation

Background and purpose: Of note,in contrast to the decreasing incidence in Western countries,lung cancer diagnosis and death in China are still rising.Non-small cell lung cancer(NSCLC)accounts for about 80%-85% of lung cancer,which is the most common histological type.Most cases have lost the opportunity of first-line surgical treatment at the time of initial diagnosis,thus mainly depends on medical treatment.Specific molecular targeted therapy for NSCLC with positive driver gene mutations has shown strong anti-tumor effect,but different gene mutations have different responses to targeted drugs.NSCLC harboring epidermal growth factor receptor(EGFR)exon 21-L858R mutation is considered to have poorer insensitivity to EGFR-Tyrosine kinase inhibitors(TKIs)than NSCLC with exon 19 deletion.So new strategies are needed to improve the efficacy of these patients.Combined EGFR-TKIs with other therapies,such as chemotherapy,radiotherapy,immunotherapy,antiangiogenic therapy and other regimens is in a vigorous clinical research,but there is no consensus on its efficacy and safety.Therefore,we retrospectively analyzed and compared the efficacy and tolerability of EGFR-TKIs combined with bevacizumab or platinum-based chemotherapy in advanced NSCLC harboring EGFR exon 21-L858R mutation,in order to provide guidance for the treatment of this poor prognosis subtype.Methods: A total of 118 eligible patients with stage Ⅳ non-squamous NSCLC harboring EGFR exon 21-L858R mutation visited our hospital from June 2016 to June 2020 were enrolled in this study.They were divided into icotinib combined bevacizumab group(abbreviated to I+A group),icotinib combined platinum-based chemotherapy group(abbreviated to I+C group)and icotinib monotherapy group(abbreviated to I group)according to first-line treatment regimen.The general clinical data such as gender,age,smoking history,ECOG score and brain metastasis were collected.The primary observed endpoints were objective response rate(ORR),disease control rate(DCR)and progression-free survival(PFS).Treatment-related adverse events were observed and compared among each group.IBM SPSS23.0 statistical software was used to analyze the data.The enumeration data were compared with χ~2 test and Fisher exact test,Kaplan-Meier was used for survival analysis,and survival curve were drawn,univariate and multivariate survival analyses were performed by log-rank and Cox regression,respectively.P < 0.05 was considered statistically significant.Results: 1.Among 118 patients of advanced NSCLC harboring EGFR exon 21-L858R mutation included in this study,there were 40 patients in I group,40 patients I+A group and 38 patients I+C group.There was no statistical significance in gender,age,smoking history,ECOG score and brain metastasis among the three groups.2.The ORR was 35.0%,52.5%,57.5%,while the DCR was 80.0%,90%,86.8% respectively in I groups,I+A group and I+C group,and there were no statistically significant differences in ORR and DCR among the three groups(P = 0.105,P = 0.429).3.The PFS of I group,I+A group and I+C group was 8 months,12 months,and 14 months respectively.The PFS of I+A group and I+C group was superior to T group,and the difference has statistical significance(P=0.011 P<0.01).4.Univariate analysis showed that brain metastasis,ECOG score could affect PFS,while multivariate analysis showed that brain metastasis was independent poor prognostic factors of PFS.5.There was a statistically significant difference of myelosuppression,gastrointestinal reactions,while abnormal liver function,proteinuria,hypertension,haemorrhage,rash and loss of appetite has no statistically significant difference between I group,I+A group and I+C group.The incidence of myelosuppression and gastrointestinal reactions in the in I+C group was higher than I group and I+C group,there were no statistically significant differences of all grade 3-4 adverse reactions among the three groups.Conclusion: 1.Both icotinib combined with bevacizumab or platinum-based chemotherapy could improve the PFS of advanced non-squamous NSCLC patients who harboring EGFR exon 21-L858 R mutation.Although icotinib combined with platinum-based chemotherapy increased the overall adverse events rate,toxicity is controllable.2.Brain metastasis is independent poor prognostic factor of PFS for advanced non-squamous NSCLC patients who NSCLC harboring EGFR exon 21-L858R mutation.