| Objective:Epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKIs)has become the standard choice for treating non-small cell lung cancer(NSCLC)patients with EGFR sensitive mutations.However,many retrospective analyses have found that the sensitivity of icotinib to exon 19 deletion and exon 21 point mutation(L858R)is inconsistent.How to improve the efficacy of icotinib in NSCLC patients harboring exon 21-L858R mutation(L858R)and maintain better tolerance is a reality that clinicians need to solve.This study aims to explore the efficacy of doubled dose of icotinib in the treatment of advanced NSCLC patients harboring EGFR exon 21-L858R mutation,and analyze the correlation between the patient’s clinical characteristics and the clinical response simultaneously.Methods:77 advanced NSCLC patients possessed EGFR L858R mutations diagnosed by pathology in Jing County Hospital of Anhui Province,Wuhu Second Hospital,Wuhu Hospital of Traditional Chinese Medicine,and Yijishan hospital of Wannan Medical College during the period from January 2018 to May 2021 were enrolled as research subjects.Based on the research purpose,they were divided into 3 groups,respectively:Icotinib conventional dose group(21-L858R-RD,n=26),Icotinib double dose group(21-L858R-HD,n=24)and Osimertinib conventional dose group(21-L858R-Osimertinib,n=27),and followed by 2-year follow-up.The blood coagulation routine,tumor markers,vascular endothelial growth factor(VEGF)levels and progression-free survival(PFS),adverse reactions in the three groups before and after treatment were compared,the correlation between patient’s clinical characteristics(including gender,age,smoking history,family history,TNM stage at first diagnosis,tumor differentiation,chest imaging features such as the size of the lesion,CT value,lobulation and spicule,cavity sign,pleural indentation)and curative effects were analyzed.Results:After 3 months of treatment,levels of fibrinogen(FDP),CA125,carcinoembryonic antigen(CEA),CA199 and VEGF in the three groups were significantlyreduced(p<0.05).Comparedwith21-L858R-RDand21-L858R-Osimertinib,the above indicators in 21-L858R-HD group decreased more significantly,and the difference was statistically significant(p<0.05).The disease control rate of the 21-L858R-HD group was significantly higher than the other two groups(X~2=8.242,p=0.016).The average progression-free survival(m PFS)in the three groups were:9.14 months in 21-L858R-RD group,12.84 months in 21-L858R-HD group,9.65 months in 21-L858R-Osiminib group,respectively;m PFS in 21-L858R-HD group was significantly higher than that in 21-L858R-RD,21-L858R-Osimertinib group,the difference was significant(X~2=36.000,p=0.000).In the multivariate Cox proportional hazard regression model,mutation abundance,tumor stage,thick-walled cavity,lesion diameter,brain metastasis,and weight loss served as covariates.Multivariate analysis showed that in addition to tumor stage,ECOG scores and brain metastasis being related to PFS in patients with advanced tumors,the diameter of lesions>3cm(HR=7.049,95%CI=1.373-8.200,p=0.008)was an independent predictor of PFS.m PFS in the three groups were compared according to the size of the lesion(>3cm and≤3cm).Among them,PFS in 21-L858R-RD(7.133m vs10.763m),21-L858R-HD(10.080m vs 13.375m),21-L858R-Osiminib(8.403m vs10.63m).Compared with the 21-L858R-RD group,higher incidence of diarrhea and leukopenia were seen in the 21-L858R-HD group,but most of them were grade 1 or 2,and serious adverse events were rare.Conclusion:Compared with the conventional dose of icotinib,advanced NSCLC patients with 21-L858R mutation have better clinical efficacy and tolerable toxicity after the administration of icotinib with double dose.Apart from tumor stage,ECOG scores,and brain metastasis being related to PFS in patients with advanced tumors,the diameter of lesions>3cm is an independent predictor of PFS in patients with EGFR mutations. |
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