Randomized Phase III Trial of Platinum-Doublet Chemotherapy Followed by Gefitinib Compared With Continued Platinum-Doublet Chemotherapy in Japanese Patients With Advanced Non-Small-Cell Lung Cancer: Results of a West Japan Thoracic Oncology Group Trial (WJTOG0203)
Randomized Phase III Trial of Platinum-Doublet Chemotherapy Followed by Gefitinib Compared With Continued Platinum-Doublet Chemotherapy in Japanese Patients With Advanced Non-Small-Cell Lung Cancer: Results of a West Japan Thoracic Oncology Group Trial (WJTOG0203)
复制标题
DOI：
10.1200/jco.2009.23.3445
复制
发表时间：
2010-02-10
影响因子：
45.3
通讯作者：
Fukuoka, Masahiro
中科院分区：
文献类型：
--
作者：
Takeda, Koji;Hida, Toyoaki;Fukuoka, Masahiro
吉非替尼是一种表皮生长因子受体酪氨酸激酶的小分子抑制剂。我们进行了一项III期试验，以评估吉非替尼是否改善晚期非小细胞肺癌（NSCLC）患者铂双联化疗后的序贯疗法的生存率。患者和方法未经化疗的晚期（IIIB/IV）NSCLC患者，东部肿瘤协作组的体能状态为0至1，和足够的器官功能被随机分配到铂双联化疗最多6个周期（A组）或铂双联化疗3个周期，然后口服吉非替尼250 mg每日一次，直至疾病进展（B组）。患者按疾病分期、性别、组织学和化疗方案分层。主要终点是总生存率;次要终点包括无进展生存率、肿瘤反应、安全性和生活质量。结果2003年3月至2005年5月，604例患者被随机分配。B组的无进展生存期有统计学显著性改善（风险比[HR]，0.68; 95% CI，0.57 - 0.80; P = 0.001）;然而，总生存期结果未达到统计学显著性（HR，0.86; 95% CI，0.72 - 1.03; P = 0.11）。在对组织学组的总生存率进行的探索性亚组分析中，B组腺癌患者明显优于A组腺癌患者（n = 467; HR，0.79; 95%CI，0.65 - 0.98; P = 0.03）。探索性亚组分析表明，吉非替尼序贯治疗可能延长生存期，尤其是腺癌患者。
PurposeGefitinib is a small molecule inhibitor of the epidermal growth factor receptor tyrosine kinase. We conducted a phase III trial to evaluate whether gefitinib improves survival as sequential therapy after platinum-doublet chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC).Patients and MethodsChemotherapy-naive patients with advanced stage (IIIB/IV) NSCLC, Eastern Cooperative Oncology Group performance status of 0 to 1, and adequate organ function were randomly assigned to either platinum-doublet chemotherapy up to six cycles (arm A) or platinum-doublet chemotherapy for three cycles followed by gefitinib 250 mg orally once daily, until disease progression (arm B). Patients were stratified by disease stage, sex, histology, and chemotherapy regimens. The primary end point was overall survival; secondary end points included progression-free survival, tumor response, safety, and quality of life.ResultsBetween March 2003 and May 2005, 604 patients were randomly assigned. There was a statistically significant improvement in progression-free survival in arm B (hazard ratio [HR], 0.68; 95% CI, 0.57 to 0.80; P = .001); however, overall survival results did not reach statistical significance (HR, 0.86; 95% CI, 0.72 to 1.03; P = .11). In an exploratory subset analysis of overall survival by histologic group, patients in arm B with adenocarcinoma did significantly better than patients in arm A with adenocarcinoma (n = 467; HR, 0.79; 95% CI, 0.65 to 0.98; P = .03).ConclusionThis trial failed to meet the primary end point of OS in patients with NSCLC. The exploratory subset analyses demonstrate a possible survival prolongation for sequential therapy of gefitinib, especially for patients with adenocarcinoma.