Background and objective: The Expand Access Program (EAP) of Iressa(gefitinib, ZD1839) in China was initiated in 2001 with the aim of providing gefitinib to non-small cell lung cancer (NSCLC) patients who failed to respond to standard treatment or who could not tolerate chemotherapy. The primary objective was to describe the quality of life (QoL), tumor control status, drug safety, and clinical/genomic features of active long-term survivors enrolled in the EAP. The secondary objective was to determine the clinical characteristics of long-term survivors in the EAP program.
Methods: In this descriptive observational study, data were collected based on epidemiological research methods. The data of patients who were actively participating in the EAP and still undergoing gefitinib treatment were collected in a cross-sectional manner to reflect the current status of each patient. Meanwhile, the data of patients who had been on gefitinib treatment for more than three years and had already been terminated from the EAP or those who were fast progressors were collected retrospectively.
Results: A total of 934 patients were screened in the EAP database. Among these patients, 25 were active long-term survivors still enrolled in the EAP and 34 were long-term survivors who had been terminated from the program. These 59 patients were enrolled in 15 different centers in China, and the remaining 875 patients were fast progressors. The median scores for the Functional Assessment of Cancer Therapy-Lung (FACT-L), Trial Outcome Index (TOI), and Lung Cancer Subscale (LCS) of the 25 long-term survivors were 64.5, 37 and 12.5, respectively. The performance status 0-1 accounted for 91.6% of the data observed during the cross-sectional survey. For active long-term survivors, the objective response rate was 37.5%, the disease control rate was 87.5%, and the median duration of response time was almost 68 months. In the long-term survivor group, no serious and new adverse events were reported. Patients who were aged under 65 years (68.5%), affected with adenocarcinoma (81.4%), female (55.9%), or had never smoked (71%) accounted for majority of the long-term survivors. The percentage of females was significantly higher in the long-term survivor group than in the fast progressor group (P=0.02). Three tissue samples were collected from each of the 24 active long-term survivors, and one patient was found to be positive of EGFR mutation. Twenty-two blood samples were also collected, and one patient tested positive for EGFR mutation. The Ki67 protein expression was also tested in three tissue samples, and two of these were found positive for Ki67 protein expression, with a response duration time of over 73 months.
Conclusions: A 250 mg dose of gefitinib offers good QoL and is safe for advanced NSCLC long-term survivors even after more than three years of treatment. According to the evaluation of the current tumor control statuses of patients, gefitinib demonstrates good efficacy in these active long-term survivors.
背景与目的: 中国易瑞沙（吉非替尼、ZD1839）扩大用药（EAP）项目开始于2001年，旨在为标准治疗失败后或不能耐受化疗的晚期非小细胞肺癌（non-small cell lung cancer, NSCLC）患者提供吉非替尼单药治疗。本研究主要评估仍在EAP组长期生存者的生活质量、肿瘤控制情况、服药安全性、临床特点及基因测定。次要目标为探讨长期生存者的临床特征。
方法: 这是一项描述性观察研究，数据收集依据流行病学研究方法。对于仍在EAP组中的患者，数据将采用横断面调查的方法；对于已从EAP组中退出的长期生存者和快速进展者，数据以回顾性方式收集。
结果: 在EAP数据库中共筛选出符合条件的患者934例，其中59例为服用吉非替尼> 3年的长期生存者，包括25例仍在EAP组，34例已退出EAP组，875例为快速进展者。59例长期生存者来自中国的15个临床中心。仍在EAP组的长期生存者，中位肺癌治疗功能评价量表（functional assessment of cancer therapy-lung, FACT-L）、试验结果系数（trial outcome index, TOI）和肺癌量表（lung cancer subscale, LCS）分值分别为64.5、37和12.5，91.6%患者的体力状态（performance status, PS）为0分-1分，客观有效率、疾病控制率和中位有效持续时间分别为37.5%、87.5%和68个月。在59例长期生存者中，没有发现严重或新的不良反应；其中 < 65岁者68.5%，腺癌81.4%，女性55.9%，从不吸烟者71%。与快速进展者比较，长期生存者中女性比例稍高（P=0.02）。本研究收集了3例患者的组织标本，其中1例EGFR突变阳性；2例Ki-67蛋白表达阳性，这2例患者生存期都超过73个月。同时收集了22例血浆标本，1例EGFR突变阳性。
结论: 部分晚期NSCLC应用吉非替尼治疗可获3年以上长期生存，并为长期生存者提供了良好的生活质量、满意的疗效和药物耐受性。
Trial registration: ClinicalTrials.gov NCT01000740.