The Relation Between EML4-ALK Fusion Gene Subtypes And Therapeutic Efficacy Of Advanced Non-small Cell Lung Cancer

ObjectThe study was to investigate the efficacy of crizotinib or pemetrexed in combination with platinum in patients with non-small cell lung cancer(NSCLC)in different echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase(EML4-ALK)fusion gene subtypes.Materials and methodsFrom August 2015 to September 2018,in the Molecular Pathology Laboratory of the Affiliated Tumor Hospital of Zhengzhou University,advanced NSCLC patients who were positive for ALK fusion gene were screened out from lung cancer patients by detection of eight driving genes Next-Generation sequencing(NGS),and their clinical data were collected.The EML4-ALK fusion gene was divided into four groups:E13:A20(variant 1,v1),E20:A20(variant 2,v2),E6:A20(variant 3,v3)and other subtypes.The primary endpoint of the study was progression free survival(PFS),the secondary endpoint is the objective response rate(ORR).Statistical analysis was performed by SPSS 21.0 software.The comparison of the count data was performed by X2 test or Fisher’s exact test.The survival analysis was performed by Kaplan-Meier method and Log-rank test.The risk ratio of 95%CIs was analyzed by multivariate Cox regression.Results1.A total of 122 ALK-positive NSCLC patients were screened.Of these,81 patients were available for statistical analysis.Among the 51 patients who received targeted therapy for the first time and the regimen was crizotinib,including 24 first-line treatments,18 second-line treatments,and 9 third-line and above treatments.Among the patients who received chemotherapy for the first time,53 patients were treated with pemetrexed plus platinum,including 44 in the first-line treatment and 9 in the second-line treatment.2.The ORR of patients with v1,v2,v3 and other variants were 55.56%(10/18),62.50%(5/8),44.44%(4/9)and 43.75%(7/16)in the first-line treatment of crizotinib,respectively;the median PFS of them were 11.96m,15.08m,12.88m,and 7.62m,respectively.There was statistically significant in PFS between v2 and other subtypes(v2 vs other subtypes=15.08m vs 7.62m;P=0.037),so did v3 and other subtypes(v3 vs other subtypes=12.88m vs 7.62m;P=0.048).There was no significant difference in PFS between the v1:v2,v1:v3,v2:v3,and v1:other variants.There was also no significant difference in PFS between the v2 and non-v2 variants(v2 vs non-v2=15.08m vs 9.10m;P=0.22).3.The ORR of patients with v1,v2,v3 and other subtypes were 41.18%(7/17),37.50%(3/8),36.36%(4/11)and 41.18%(7/17)in the first-line treatment of pemetrexed plus platinum,respectively;and the median PFS were 9.13m,3.22m,7.52m,and 7.85m,respectively.The PFS were significant differences between vi and v2(v1 vs v2-9,13m vs 3.22m;P=0.007),v2 and other subtypes(v2 vs other subtypes=3.22m vs 7.85m;P=0.015).However,there was no significant difference in PFS bet,ween v1 and v3,so did v2 vs v3,v1 vs other subtypes.The median PFS time was significantly longer in patients with varriant 1 than in those with n on-v2(median PFS,3.22m vs 7.56m,respectively;P-0.004).4.The median PFS of v2 was significantly longer in patients with crizotinib than in those with pem etrexed plus platinum(median PFS,15.08m vs 3.22m,respectively;P=0.002).Conclusion1.The efficacy of crizotinib in patients with the EML4-ALK fusion gene subtype is E20;A20(v2)is better than that of pemetrexed in combination with platinum.2.The median PFS of crizotinib in patients with the EML4-ALK fusion gene subtype of E20;A20(v2)may be longer than other subtypes,and the median PF-S with pemetrexed in combination with platinum may be shorter than other subtypes.3.Dif ferent EML4-ALK fusion subtypes might affect the efficacy of ALK inhibitors and chem otherapy.