ESMO2016：新型抗体药物MABp1显著提高晚期结直肠癌患者存活期

作者：杨超月

2016年7月5日/生物谷BIOON/--根据欧洲临床肿瘤学会（ESMO）在西班牙巴塞罗纳市举行的第18届世界胃肠道癌症大会发布的III期临床试验数据，一种新的抗白细胞介素-1α抗体MABp1（Xilonix）对晚期结直肠癌患者的症状产生显著影响，同时具有高水平的安全性和耐受性。

作为首个单克隆抗体药物，Xilonix特异性靶向和中和白细胞介素-1α（interleukin 1-alpha, IL-1α），其中IL-1α是人体或肿瘤细胞产生的最为强效的炎性分子之一。

这项临床研究的主要研究员Tamas Hickish博士说，“肿瘤中的IL-1α促进血管发生，从而有助于提供肿瘤生长所需的至关重要的血液供应，而且它也能够让体内的代谢失去控制，从而导致燃烧肌肉中的能量，减轻体重。”与此同时，IL-1α对大脑的影响能够导致与晚期癌症相关联的疲劳、焦虑和厌食。

在这项临床研究中，研究人员招募了309名转移性结直肠癌患者，其中这些患者并不对奥沙利铂（oxaliplatin）和伊立替康（irinotecan）的标准化疗药物作出反应，并且表现出较高严重程度的症状、功能性损伤、体重减轻或较高水平的全身性炎症。

除了利用这种新的试剂进行临床试验外，研究人员也针对基于症状控制的客观反应制定出新的策略，而且是与欧洲药品管理局（EMA）科学咨询工作组合作制定出来的。这些策略与双能X线吸收计量法和EORTC-QLQC30联合使用以便评估疾病控制措施。

这些患者按照2:1的比例进行随机分配接受MABp1或安慰剂治疗，除此之外，他们都接受最好的支持性护理。

接受MABp1治疗与临床反应率（clinical response rate）上的76%的显著相对增加相关联。表现出临床反应的患者存活期（11.5个月）几乎是那些没有产生反应的患者（4.2个月）的3倍。

研究人员也发现改善的健康状态指标与几乎所有其他的自我报道的和实验室测量的健康指标改善---包括改善的肿瘤相关白细胞活性控制和降低的全身性炎症---相关联。

相比于安慰剂治疗，MABp1治疗方案的严重不良事件也下降了四分之一。

Hickish博士说，“这些数据提示着Xilonix具有良好的耐受性，而且有潜力为晚期结直肠癌患者开发出更加有效的毒性更少的疗法。”

“这项研究也提供首个证据证实健康状态实际上能够被用来测量针对难治的晚期结直肠癌的抗肿瘤疗法的疗效，以及基于健康状态的临床反应能够是总生存期益处的一个预测因子。”（生物谷 Bioon.com）

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Anti-interleukin-1 alpha antibody MABp1 improves outcomes significantly over placebo

BARCELONA-LUGANO – A novel anti-interleukin 1-alpha antibody has shown a significant impact on symptoms, and a high level of safety and tolerability in patients with advanced colorectal cancer, according to phase III data (1) presented at the European Society for Medical Oncology’s 18th World Congress of Gastrointestinal Cancer in Barcelona, Spain.

Xilonix is the first monoclonal antibody immunotherapy to specifically target and neutralize interleukin-1 alpha (IL-1α), one of the most potent inflammatory substances manufactured by the body or tumour cells.

“IL-1α in tumours promotes angiogenesis, helping to provide crucial blood supply for tumour growth, and it can also send the body’s metabolism out of control, causing it to burn muscle and lose weight,” said lead investigator Dr Tamas Hickish. At the same time, IL-1α effects on the brain can cause the fatigue, anxiety and anorexia associated with advanced cancer.

The study enrolled 309 patients with metastatic colorectal cancer whose disease had not responded to standard chemotherapy with oxaliplatin and irinotecan and who showed a high degree of symptoms, functional impairment, weight loss or elevated systemic inflammation.

In addition to trialing the new agent, researchers also implemented new criteria for objective response based on control of symptoms, which were developed in collaboration with the European Medicines Agency’ Scientific Advice Working Group. These criteria were applied in conjunction with dual-energy X-ray absorptiometry and EORTC-QLQC30 to assess disease control.

Patients were randomized them in a 2:1 ratio to MABp1 with best supportive care, or placebo and the same.

Treatment with MABp1 was associated with a significant 76% relative increase in clinical response rate. Patients who showed a clinical response lived almost three times as long as those who did not respond (11.5 months vs. 4.2 months).

Researchers also found that measures of improved health status correlated with improvement in almost all other self-reported and laboratory-based measures of health, including with improved control of tumor-related white blood cell activity and reduced systemic inflammation.

There were also one-quarter fewer serious adverse events in the treatment arm of the study compared to placebo.

“These data suggest Xilonix is very well tolerated, and has the potential to meet the real and urgent need for more effective, less toxic therapies for patients with advanced colorectal cancer,” Dr Hickish said.

“This study also provides the first evidence that health status can actually be used to measure efficacy of anti-tumour therapy in advanced, refractory colorectal cancer, and that clinical responses based on health status can be a predictor of overall survival benefit.”