Efficacy Of Crizotinib In Advanced EML4-ALK Positive Non-small Cell Lung Cancer

Objective The clinical efficacy and adverse reactions of Crizotinib in Chinese patients are still lack of large clinical trials,The purpose of this study is :1?Study efficacy and adverse effects of crizotinib in advanced Echinoderm microtubule-assciated protein-like 4 Anaplastic lymphoma kinase(EML4-ALK)fusion gene positive non-small cell lung cancer.2?Contrast the efficacy and adverse effects of Crizotinib in EML4-ALK fusion gene positive non-small cell lung cancer with the traditional standard chemotherapy regimen.3?To study the clinical efficacy and adverse effects of Crizotinib in advanced EML4-ALK positive non-small cell lung cancer.Method 1?45 patients with EML4-ALK fusion gene positive NSCLC were enrolled in this study,treated with Crizotinib,250 mg,twice daily,oral,until progressive disease(PD)or the occurrence of adverse reactions can not be tolerated,the follow-up period was 12 month s.To observe the efficacy and tolerance of Crizotinib.2?86 Patients with EML4-ALK fusion gene positive NSCLC were enrolled to the Crizotinib group and the traditional standard chemotherapy group,each group had 43 cases.The follow-up period was 12 months.The efficacy and toxicity of the Crizotinib group were analysised in compared with traditional standard chemotherapy group.3?20 patients with EML4-ALK fusion gene positive NSCLC with brain metastasis were enrolled,treated with Crizotinib,250 mg,twice a day,oral,until PD or the occurrence of adverse reactions can not be tolerated,the follow-up period was 12 months.To observe the efficacy and tolerance of Crizotinib.Result 1?Efficacy of crizotinib in advanced ALK positive non-small cell lung cancerNSCLC patients with EML4-ALK positive were treated with Crizotinib for at least one month,and the curative effect was evaluated after one month.Crizotinib partial response(PR)was 60%(27/45),stable disease(SD)was 34.9%(15/45),disease progression(PD)was 6.7%(3/45),objective response rate(ORR)was 60.5%(26/43),disease control rate(DCR)was 94.9%(42/45),median progression free survival(PFS)was 7 months.There was no significant difference in age,gender,smoking history,the status of EGFR gene and whether first-line treated Crizotinib.The effect of oral Crizotinib after chemotherapy in this group was significantly better than that in the group of patients who did not receive chemotherapy(median PFS was 8 months VS 5 months,the difference between the two groups was statistically significant).The adverse reactions taking the incidence of Crizotinib was 40%(18/45),the main adverse reactions were nausea,constipation and visual impairment,elevated alanine aminotransferase,1 patients during oral Crizotinib treatment had III degree of bone marrow suppression,after symptomatic treatment,blood restored to normal and continue oral Crizotinib,all the patients can terminate the tolerance to treatment.2?Efficacy comparison between Crizotinib and chemotherapy for patients with NSCLCCrizotinib group: CR was 0,PR was 60.5%(26/43),SD was 32.6%(14/43),PD was 7%(3/43),ORR was 60.5%(26/43),DCR was 93%(40/43),and median PFS was 7 months.Chemotherapy group: CR was 0,PR was 25.6%(11/43),SD was 20.9%(9/43),PD was 53.5%(23/43),ORR was(11/43),DCR was 46.5%(20/43),median PFS was 3 months.Patients in the Crizotinib group were significantly better than the traditional standard chemotherapy group,P=0.015,the difference between the two groups was statistically significant.The incidence of adverse reactions in Crizotinib group was 41.8%(18/43),the main adverse reactions to visual disorder,nausea,constipation and elevated alanine aminotransferase,1 patients during oral Crizotinib treatment had III degree of bone marrow suppression,after symptomatic treatment to restore normal blood and continue oral Crizotinib,all patients were able to terminate the tolerance to treatment.The main adverse reactions in the standard chemotherapy group were alopecia,nausea,vomiting,diarrhea,and alanine aminotransferase,4 patients in the chemotherapy group were unable to tolerate chemotherapy for severe chemotherapy.1 patients died during intermission of chemotherapy.3?Efficacy analysis of crizotinib for brain metastases in ALK positive non-small cell lung cancer20 cases of advanced NSCLC have occurred brain metastasis in patients with EML4-ALK fusion gene positive treated with Crizotinib at least one month,Clinical analysis showed: CR 0,PR 60%(12 /20),SD 45%(7/20),PD 5%(1/20).ORR was 60%(12/20)and DCR was 95%(19/20).At the end of follow-up,there were 16 patients who progressed,and the first progression was intracranial progression 62.5%(10/16).In this group of patients without radiotherapy was 20%(4/20),Radiotherapy or brain metastases surgery 80%(16/20).in patients without radiotherapy,SD was 75%(3/4),PR was 25%(1/4),ORR was 25%(1/4),DCR was 100%(4/4).In 16 patients treated with radiotherapy or brain metastases,SD 31.2%(5/16),PR 62.5%(10/16),PD 6.25%(1/16),ORR was 62.5%(10/16),DCR was 93.8%(15/16)?The m PFS was 7 months(95% CI 5.70-8.30 months)for patients treated with radiotherapy or brain metastases in the study group,significantly longer than those who did not receive radiotherapy or surgery(P=0.003).13 patients treated with gamma knife before Crizotinib,including whole brain radiotherapy(WBRT),stereotactic radiotherapy(SBRT)and surgery,the median PFS was 7 months(95% CI 4.74-9.26),3 cases treated radiotherapy after taking Crizotinib,m PFS was 6 months.There was no significant difference in Crizotinib before or after radiotherapy(P=0.951).The adverse reaction incidence rate of Crizotinib was 40%(8/20),included visual disorder,nausea,constipation,and elevated alanine aminotransferase,1 patients during oral Crizotinib treatment had III degree of bone marrow suppression and after symptomatic treatment,blood restored to normal and can continue to oral Crizotinib,all the patients were able to tolerate and adhere to the end of treatment.Conclusion1?As the first approved in advanced EML4-ALK positive non-small cell lung cancer targeted drug therapy,Crizotinib has significant curative effects,adverse reactions were in the tolerable range.2?Compared with the traditional standard,Crizotinib in treating NSCLC patients with EML4-ALK fusion gene positive has significant curative effects.It can appreciately prolong the m PFS of patients and raise NSCLC patients quality of lives,toxicity is lower than chemotherapy.Crizotinib targeted therapy should be preferred in patients with EML4-ALK fusion gene positive NSCLC.3?Crizotinib also showed effective control for patients with EML4-ALK fusion gene positive NSCLC who had brain metastases.