The aim of this study was to investigate the molecular characteristics of each subtype of the EML4-ALK fusion gene and to evaluate the efficacy of first-line crizotinib or pemetrexed in combination with platinum in the treatment of patients with advanced NSL4-ALK fusion subtypes of advanced NSCLC. From August 2015 to September 2018, the clinicopathological data of patients who received driver genes detection for lung cancer in the Affiliated Cancer Hospital of Zhengzhou University were collected, NGS was used for gene detection. The EML4-ALK fusion gene was divided into E13: A20 subtype (variant 1, V1), E20: A20 subtype (variant 2, V2), E6: A20 subtype (variant 3, V3) and Other subtypes (V4) 4 groups. The primary study endpoint was progression-free survival. A total of 122 patients with ALK fusion gene-positive NSCLC were screened. Of the 122 patients, 41 (33.6%) had V1 variants, 14 (11.5%) had V2 variants, 35 (28.7%) had V3 variants, and 32 (26.2%) had other variants. There was no correlation between EML4-ALK gene mutation subtypes and distant metastasis (x2=0.570, P=0.903), brain metastasis (x2=4.447, P=0.217) and bone metastasis (x2=1.547, P=0.672). The median was 13.3 months (95% CI: 9.45-17.10) and 6.83 months (95% CI: 5.30-8.36), respectively, in patients receiving first line Crizotinib and chemotherapy, with statistically significant differences (P =0.001). In the first-line application of crizotinib, the ORR of V1, V2, V3 and V4 variants were 55.56% (10/18), 62.50% (5/8), 44.44% (4/9) and 43.75%, respectively. (7/16), median PFS were 11.96 months, 15.08 months, 12.88 months, and 7.62 months, respectively. There was no significant difference. The ORR of V1, V2, V3 and V4 variants in first-line patients treated with pemetrexe-platinum regimen was 41.18% (7/17), 37.50% (3/8), 36.36%(4/11)and 41.18% (7/17), respectively. The median PFS were 9.13 months, 3.22 months, 7.52 months, and 7.85 months, respectively. There was no statistically significant difference in PFS between V1: V3, V2: V3, and V1: V4. However, the PFS differences in the V1:V2 group (V1:V2=9.13 months: 3.22 months, P=0.007) and the V2:V4 group (V2:V4=3.22 months: 7.85 months, P=0.015). Among all ALK fusion subtypes, E13:A20 subtype (V1 variants) is the most common. Smoking history was a factor affecting crizotinib PFS. Compared with chemotherapy, patients with E20:A20 subtype (V2 variant) showed significant benefit with crizotinib. The median PFS of the pemetrexed combined with platinum regimen was lower than that of the E13:A20 subtype.
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