法米替尼治疗晚期转移性结直肠癌II期临床研究2015ASCO会议

2015年ASCO GI研讨会将于1月15日-17日在美国旧金山举行。在1月17日（周六）的口头报告专场，广州中山大学肿瘤医院徐瑞华教授将带来关于法米替尼治疗晚期结直肠癌II期研究的精彩报告（摘要号#513）。下面提前和大家分享这项研究：山东省医学科学院附属医院肿瘤内科刘蒲香

研究背景

结直肠癌（CRC）是第三大常见的癌症，在中国癌症死亡的原因中排第五位。对于二线治疗失败后的晚期CRC患者目前没有标准的治疗方案。法米替尼是一个小分子的多靶点受体酪氨酸激酶抑制剂，主要通过抑制血管生成发挥作用。这项II期研究旨在评估法米替尼治疗晚期结直肠癌的疗效和安全性。

研究方法

这是一项多中心、随机、双盲、安慰剂对照的II期临床研究（临床试验注册号：NCT01762293）。研究共纳入154例二线或二线以上治疗失败的晚期结直肠癌患者，按照2：1随机分配接受法米替尼或安慰剂，25mg/天/周期。主要试验终点为无进展生存期（PFS），次要试验终点包括总生存期（OS），客观缓解率（ORR），疾病控制率（DCR），生活质量（QoL）和安全性。使用意向治疗人群进行试验终点的统计分析。

研究结果

154例随机分组的患者中，治疗组和对照组中位无进展生存期（mPFS）分别为2.8个月和1.5个月（P =0.0034; HR=0.58），ORR分别为2.02％和0.00％（p=0.54），DCR分别是57.58％和30.91％（p=0.0023）。对OS数据的分析正在进行中。常见的不良事件（AE）包括中性粒细胞减少、血小板减少、高血压、蛋白尿和手足综合征，多数是1/2级。严重不良事件（SAE）在法米替尼组和安慰剂组的发生率分别为11.11％和9.09％（p=0.7884）。总体而言，法米替尼耐受性良好，毒性可控。

结论

法米替尼改善了晚期转移性结直肠癌患者的PFS，提高治疗组的ORR和DCR，具有良好的安全性和耐受性。

英文摘要

A randomized, double-blind, parallel-group, placebo-controlled, multicenter, phase II clinical study of famitinib in the treatment of advanced metastatic colorectal cancer.（Abstract No:513）

Background: Colorectal cancer (CRC) is the third most frequently diagnosed cancer and is the fifth leading cause of cancer death in China. No standard care is available for patients with advanced CRC who failed the second-line treatment. Famitinib is a small-molecular, multi-target receptor tyrosine kinase inhibitor which primarily acts against angiogenesis. This phase II study was designed to evaluate the efficacy and safety of famitinib in the treatment of advanced colorectal cancer. 

Methods: This is a multi-center, randomized, double-blind, placebo-controlled, phase II clinical study (ClinicalTrials.gov Registration No.: NCT01762293). Totally 154 patients with advanced colorectal cancer who failed second or later-line treatments were randomized in a 2:1 ratio to receive either famitinib or placebo at 25 mg each day in each treatment cycle. The primary endpoint was progression-free survival (PFS), and the secondary endpoints include overall survival (OS), objective response rate (ORR), disease control rate (DCR), quality of life (QoL) and safety. The statistical analyses of endpoints were using intent-to-treat population. 

Results: Of 154 patients randomized, the mPFS was 2.8 and 1.5 months in the treatment group and control group, respectively (p=0.0034; HR=0.58). The ORR was 2.02% and 0.00% (p=0.54) and the DCR was 57.58% and 30.91% (p=0.0023) in the treatment group and control group, respectively. Analysis of OS data is ongoing. The frequently reported adverse events (AEs) include neutropenia, thrombocytopenia, hypertension, proteinuria, and hand-foot syndrome and were most grade 1/2. The incidences of serious adverse events (SAEs) for the famitinib and placebo groups were 11.11% and 9.09%, respectively (p=0.7884). Overall, famitinib was well tolerated and toxicities were manageable. 

Conclusions: Famitinib improved the PFS in patients with advanced metastatic colorectal cancer resulting in higher ORR and DCR in the treatment group with good safety and tolerability. 

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