[Association between the ALK Gene Status and the Efficacy of First-line Pemetrexed Chemotherapy in Patients with Advanced Lung Adenocarcinoma]

[ALK基因状态与晚期肺腺癌患者一线培美曲塞化疗疗效的相关性]

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Abstract

BACKGROUND: Anaplastic lymphoma kinase (ALK) is one of the major driver genes of non-small cell lung cancer (NSCLC). Several studies have shown that the efficacy of pemetrexed in ALK-positive lung cancer is controversial. The aim of this study is to explore the efficacy of pemetrexed-based chemotherapy in patients with ALK-positive and negative lung adenocarcinoma. METHODS: The clinical data of 98 cases of epidermal growth factor receptor (EGFR), kirsten rat sarcoma viral oncogene (KRAS), V-rafmurine sarcoma viral oncogene homolog B1 (BRAF)-negative patients with advanced lung adenocarcinoma patients who diagnosed by histopathology from January 2015 to April 2016 in the First Affiliated Hospital of Zhengzhou University were collected. The relationships between ALK gene status, clinical characteristics and response and progression-free survival (PFS) were analyzed. RESULTS: All of the 98 patients' ALK status were determined. ALK gene fracture fusion occured in 34 cases (34.7%), no fracture fusion in 64 cases (65.3%). All patients underwent first-line pemetrexed and platinum-based chemotherapy, the objective response rate (ORR) was 21.4% and the disease control rate (DCR) was 84.7%. The ORR and DCR of patients with ALK fracture fusion were higher than those without fracture fusion (41.2% vs 10.9%, χ2=23.389, P<0.001; 91.2% vs 81.3%, χ2=4.153, P=0.042), the difference was statistically significant. ALK gene status was not related to age, gender, smoking history and clinical stage. The median PFS of ALK-positive lung adenocarcinoma was 7.1 months (95%CI: 6.1-8.1) and negative was 4.7 months (95%CI: 3.818-5.582), and the difference was statistically significant (χ2=13.269, P<0.001). Cox multivariate analysis indicates that PFS of pemetrexed combined with platinum chemotherapy was independent of gender, age, smoking, staging and platinum. ALK gene fracture fusion is an independent factor affecting PFS (HR=0.392, 95%CI: 0.243-0.634, P<0.001). CONCLUSIONS: ALK-positive lung adenocarcinoma patients with first-line pemetrexed-based chemotherapy have greater clinical benefit than ALK-negative patients.

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