P84.07 Distribution and Therapeutic Outcomes of Intergenic Sequence-ALK Fusion and Coexisting ALK Fusions in Lung Adenocarcinoma Patients

Abstract

ALK-rearranged NSCLC patients show survival benefits from ALK inhibitor. Studies about outcome were mostly focused on EML4–ALK fusion. Here, we performed next-generation sequencing (NGS) of baseline specimens from ALK-positive patients to examine the rearrangement distribution and possible correlation to therapeutic benefit. ALK-positive NSCLC patient(determined by immunohistochemistry) were screened at the West China Hospital, and NGS was performed on baseline samples. Clinical information and therapeutic outcomes were collected and retrospectively analyzed. Among the 89 patients with 22 ALK rearrangements partners, fusions of intergenic sequences with ALK were found in 15 (16.85%). Non-EML4–ALK fusions were present in 18 patients (20.22%), while EML4–ALK fusions in 71 (79.76%). Coexisting rearrangements were present in 16 patients (17.98%). Intergenic–ALK and non EML4–ALK fusions occurred at higher rates in patients with coexisting fusions (62.5% versus 6.85%, and 62.5% versus 10.96%). First-line crizotinib was administered in 41 patients, and the median progression-free survival (mPFS) was 9.7 months. No significant difference in mPFS was found between patients with or without intergenic ALK fusion (12 versus 9.6 months, p = 0.989). In the seven patients who had at least two fusions each, the mPFS was 11.9 months, compared with 9 months among the 24 patients with single (p = 0.336). No significant difference in mPFS was observed between patients with and without EML4–ALK fusions (9.6 versus 12 months, p = 0.924). The hazard ratio(HR) of gender, age and three rearrangements (EML4-, non EML4-, intergenic-ALK) were 0.47, 1.18, 1.09, 1.31, 0.96, respectively.Table 1Characteristics of enrolled patients.CharacteristicTotal (n = 90)TreatmentP valueSurgery (n = 46)Systemic therapy (n = 44)Age (median [range], years)51 (29-78)52.5 (30-78)49 (29-70)0.396Gender (cases, %)0.404Male47 (52.2)26 (56.5)21 (47.7)Female43 (47.8)20 (43.5)23 (52.3)Smoking status (cases, %)0.185Smoker6 (6.7)1 (2.2)5 (11.4)Non-smoker84 (93.3)45 (97.8)39 (88.6)Histology (cases, %)/Adenocarcinoma90 (100)46 (100)44 (100)Non-adenocarcinoma0 (0)0 (0)0 (0)ECOG performance status (cases, %)0.6890-179 (87.8)41 (89.1)38(86.4)2-411 (12.2)5 (10.9)6 (13.6)Stage (cases, %)<0.001I-III49 (54.4)46 (100)3 (6.8)IV41 (45.6)0 (0)41 (93.2)Metastasis (cases, %)<0.001Absent49 (54.4)46 (100)3 (6.8)Present41 (45.6)0 (0)41 (93.2)Brain metastasis13 (14.4)0 (0)13 (29.5)Bone metastasis24 (26.7)0 (0)24 (54.5)Multi-organ metastases20 (22.2)0 (0)20 (45.5)ALK aberrations (cases, %)0.489Rearrangement free Uncertain aberration1 (1.1)0 (0)1 (2.3)ALK rearrangement89 (98.9)46 (100)43 (97.7)Distribution of rearrangements (cases, %)Intergenic sequence-ALK fusion15 (16.9)9 (19.6)6 (14.0)0.480Non-EML4-ALK fusion18 (20.2)10 (21.7)8 (18.6)0.713EML4-ALK fusionVariant 126 (29.2)12 (26.1)14 (32.6)0.502Variant 24 (4.5)3 (6.5)1 (2.3)0.658Variant 330 (33.7)14 (30.4)16 (37.2)0.499Other variants11 (12.4)8 (17.4)3 (7.0)0.136Status of coexisting ALK fusions (cases, %)Absent73 (82.0)37 (80.4)36 (83.7)0.687Intergenic sequence-ALK fusion alone5 (5.6)2 (4.3)3 (7.0)0.938Non-EML4-ALK fusion alone8 (9.0)5 (10.9)3 (7.0)0.787EML4-ALK fusion alone60 (67.4)30 (65.2)30 (69.8)0.647Present16 (18.0)9 (19.6)7 (16.3)0.687Intergenic sequence-ALK fusion + EML4-ALK fusion6 (6.7)4 (8.7)2 (4.7)0.736Intergenic sequence-ALK fusion + non-EML4-ALK fusion1 (1.1)1 (2.2)0 (0)1.000EML4-ALK fusion + non-EML4-ALK fusion3 (3.4)1 (2.2)2 (4.7)0.953Intergenic-ALK fusion + EML4-ALK fusion+ non-EML4-ALK fusion2 (2.2)2 (4.3)0 (0)0.495Intergenic-ALK fusion + intragenic-ALK fusion + non-EML4-ALK fusion1 (1.1)0 (0)1 (2.3)0.483non-EML4-ALK fusion + non-EML4-ALK fusion3 (3.4)1 (2.2)2 (4.7)0.953 Open table in a new tab This is the first to report the occurrence rates and distribution of intergenic–ALK and coexisting of ALK fusions. Intergenic–ALK and non-EML4–ALK were more likely to coexist with other fusions. Neither the type nor number of rearrangements had a significant effect on the therapeutic benefit of treatment with crizotinib.