Tsujino Kazuyuki, Kawaguchi Tomoya, Kubo Akihito, Aono Nana, Nakao Keiko, Koh Yasuhiro, Tachibana Kazunobu, Isa Shun-Ichi, Takada Minoru, Kurata Takayasu
Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Osaka, Japan.
J Thorac Oncol. 2009 Aug;4(8):994-1001. doi: 10.1097/JTO.0b013e3181a94a2f.
Gaining a higher response rate (RR) has usually been determined as a primary end point in phase II trials evaluating the efficacy of new molecular targeted drugs. However, a relationship between clinical response and survival benefit has not been well studied in the patients treated with molecular targeted agents.
Prospective trials of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) monotherapy in non-small cell lung cancer were extracted from MEDLINE, EMBASE, and the annual meetings in 2007 of the American Society of Clinical Oncology, European Cancer Conference, and World Conference on Lung Cancer. Correlation between clinical response and survival was examined using linear regression analysis. We also tried to compare the significance of RR as surrogate markers for survival with that of disease control rate (DCR) by calculating the area under their receiver operating characteristic (ROC) curves.
We identified 24 phase II trials and 4 phase III trials with a total of 6171 patients and 30 treatment arms, including 22 arms for the gefitinib group and 8 arms for the erlotinib group. Both RR and DCR strongly correlated with median survival time (MST; p < 0.0001 and p = 0.003, respectively). In an ROC analysis, the area under the ROC curve predicting MST prolongation by RR was 0.918, which was higher than the area under the ROC curve by DCR.
We found a significant relationship between RR and MST in clinical trials with EGFR-TKIs. RR could be an independent surrogate marker for MST in the current response criteria in the clinical trials of EGFR-TKIs.
在评估新型分子靶向药物疗效的II期试验中，通常将获得更高的缓解率（RR）确定为主要终点。然而，在接受分子靶向药物治疗的患者中，临床缓解与生存获益之间的关系尚未得到充分研究。
从MEDLINE、EMBASE以及2007年美国临床肿瘤学会年会、欧洲癌症大会和世界肺癌大会中提取非小细胞肺癌表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）单药治疗的前瞻性试验。使用线性回归分析检验临床缓解与生存之间的相关性。我们还通过计算疾病控制率（DCR）和RR作为生存替代标志物的受试者操作特征（ROC）曲线下面积，比较两者的意义。
我们确定了24项II期试验和4项III期试验，共6171例患者和30个治疗组，其中吉非替尼组22个组，厄洛替尼组8个组。RR和DCR均与中位生存时间（MST）密切相关（分别为p < 0.0001和p = 0.003）。在ROC分析中，RR预测MST延长的ROC曲线下面积为0.918，高于DCR的ROC曲线下面积。
我们发现在EGFR-TKIs的临床试验中，RR与MST之间存在显著关系。在EGFR-TKIs的临床试验当前缓解标准中，RR可能是MST的独立替代标志物。
