Clinical Efficacy Of Osimertinib In Advanced Non-small Cell Lung Cancer

Background:Lung cancer remains the leading morbidity and mortality in the world today.For the treatment of lung cancer,traditional methods,including surgery,radiotherapy and chemotherapy,can obtain a certain efficacy--it can benefit patients and prolong the survival.However,it will also bring about a series of adverse events at the same time,which will bring a lot of pain and seriously lower the patients’ quality of life.In recent years,targeted therapy has achieved rapid development,because of its ease of use,minor side effects,high specificity and good patient tolerance.It has now become the mainstream of research in the world today.The study of epidermal growth factor receptor(EGFR)pathway has become a model for accurate treatment of lung cancer.EGFR is a very important molecule of malignant tumor of epidermal origin.Its activity is closely related to the occurrence and development of tumors.Point mutations in exon 19 and exon 21 are common mutations in two sensitive genes.Targeted therapeutic drugs for positive lung cancer patients have developed rapidly,with the first generation of representative drugs gefitinib,Rotinib,Eclatinib,second-generation Afatinib,Dacomitinib,up to the current generation of the drug Osimertinib.Although one-and two-generation molecular-targeted drugs can significantly prolong the median survival time,a large number of patients will eventually lead to drug resistance.T790 M mutation,accounting for approximately 60% of the resistance cases,is presently the most common acquired resistance mechanism for first-generation EGFR-TKIs.In order to investigate the efficacy and side effects of the third-generation drug Osimertinib for T790 M mutation,AURA series of studies were conducted.The AURA1 study showed that 127 patients with a positive T790 M mutation had an ORR of 61% and a median progression-free survival of 9.6 months.The AURA2 study showed a median progression-free survival of 13 months and an ORR of 70%.The results of the AURA3 series of studies showed that the median survival of the Osimertinib group was 10.1 months compared with the platinum-containing drug chemotherapy whose median survival was only 4.4 months.Among 144 patients who suffered from metastases to the central nervous system,the median progression-free survival in Osimertinib group was longer than the platinum plus pemetrexed group(8.5 months vs.4.2 months).These three series of studies also objectively demonstrated that the efficacy of Osimertinib in patients with advanced non-small cell lung cancer T790 M mutation positive.However,there are not many Chinese patients included in the AURA series of studies.This article focuses on the efficacy and adverse reactions of Osimertinib in late-stage T790M-positive NSCLC patients in China.Objectives:1.To investigate the efficacy and safety of third-generation TKI drug Osimertinib in domestic patients by observing the adverse reactions and non-progressive survival after EGFR gene detection with T790 M positive.2.To compare the efficacy of taking Osimertinib with T790 M positive patients and those who have not been genetically tested for there are still some patients in the clinical group who are not taking their own gene tests before they take Osimertinib.3.To compare the efficacy of Osimertinib in patients with and without brain metastases and compare the efficacy of genetic test with tissue and body fluid samples from different sources by performing stratified analysis in T790 M positive patients.Methods:A total of 35 patients with advanced non-small cell lung cancer(NSCLC)who were admitted to our department from January 2015 to December 2016 were collected.Among them,7 patients had no genetic test before treatment;25 patients were T790 M positive,testing by tissue in 13 cases and body fluids in 12 cases(11 cases in blood,1 case of pleural effusion);3 cases of T790 M negative patients’ baseline information,medication status,adverse reactions and other relevant clinical data were collected,and patients Follow-up visits were performed to observe the efficacy and adverse reactions after drug administration and statistical analysis was performed.Results:Among the 25 T790 M positive patients,the most common side effects were skin rash,thrombocytopenia,diarrhea,Q-T interval prolongation of electrocardiogram,and no fatal adverse events were observed.T790 M positive patients in 25 cases,objective remission rate: 60%,disease control rate: 88%;17 patients with positive T790 M and brain metastasis objective remission rate of 64%,disease control rate of 82%.Twenty-one patients were followed up for more than half a year,and 66% of patients had response duration exceeding 6 months.Conclusions:1.Three-generation TKI drug Osimertinib is effective in the treatment of T790 M positive patients detected by EGFR gene test,which can prolong the patient’s progression-free survival and demonstrate high safety,good tolerability and low adverse events rate.2.According to the gene detection,T790 M positive patients’ efficacy is much better than the patients who didn’t do gene test.It is recommended to clear the results of genet test before the administration of targeted therapy.3.The efficacy of Osimertinib in patients with brain metastases is significant.The results of liquid biopsy and tissue test have showed consistency in the selection of test specimens.