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.
背景与目的 间变性淋巴瘤激酶（anaplastic lymphoma kinase, ALK）是非小细胞肺癌（non-small cell lung cancer, NSCLC）的重要驱动基因之一，多项研究显示培美曲塞在ALK阳性肺癌中的疗效存在争议。本研究旨在继续探索以培美曲塞为基础的化疗在ALK阳性和阴性肺腺癌患者中的疗效。方法 回顾性分析郑州大学第一附属医院2015年1月-2016年4月经组织病理学证实的98例表皮生长因子受体（epidermal growth factor receptor, EGFR）、鼠类肉瘤病毒癌基因（kirsten rat sarcoma viral oncogene, KRAS）、鼠类肉瘤滤过性毒菌致癌同源体B1（V-rafmurine sarcoma viral oncogene homolog B1, BRAF）均为阴性的晚期肺腺癌患者的临床资料。分析ALK基因状态、临床特征、化疗疗效及无疾病进展生存期（progression-free survival, PFS）之间的关系。结果 98例患者均进行了ALK基因检测，ALK基因断裂融合34例（34.7%），未发生断裂融合64例（65.3%）。全部患者均接受一线培美曲塞联合铂类的化疗，客观缓解率（objective response rate, ORR）为21.4%，疾病控制率（disease control rate, DCR）为84.7%。ALK阳性肺腺癌患者的ORR和DCR均高于阴性患者（41.2% vs 10.9%, χ2=23.389, P<0.001; 91.2% vs 81.3%, χ2=4.153, P=0.042），差异有统计学意义。ALK基因状态与年龄、性别、吸烟史、临床分期均无明显关系。ALK阳性肺腺癌的中位PFS为7.1个月（95%CI: 6.1-8.1），阴性4.7个月（95%CI: 3.818-5.582），二者的PFS差异有统计学意义（χ2=13.269, P<0.001）。Cox回归多因素分析显示：培美曲塞联合铂类化疗的PFS与性别、年龄、吸烟、分期、与铂类药物的种类均无明显关系，ALK基因断裂融合是PFS相关的唯一变量（HR=0.392, 95%CI: 0.243-0.634, P<0.001）。结论 ALK阳性相比ALK阴性肺腺癌患者一线应用以培美曲塞为基础的化疗有更大的临床获益。.
Keywords: ALK; First-line chemotherapy; Fracture fusion gene; Lung neoplasms; Pemetrexed.