研究：Lenvatinib提高了甲状腺癌患者的生存期

In a pivotal Phase III study led by researchers at MD Anderson Cancer Center, the oral anti-angiogenic therapy lenvatinib has shown dramatic improvement in progression-free survival in patients with advanced radioiodine-refractory thyroid cancer.

全球研究为首史蒂芬一谢尔曼，医学博士, associate vice-provost for Clinical Research and chair ofEndocrine Neoplasia and Hormonal Disorders发表在新英格兰医学杂志，并且可以提供一种新的治疗模式的一组患者对他们来说，直到最近，出现了自1940年以来没有新的有效的治疗方法。初步研究结果首次在临床肿瘤学年度会议在去年的美国社会报道;在发表的研究包括更新的数据。

根据美国癌症协会，62450人将在2015年被诊断为甲状腺癌，并且1,950将死于这种疾病。它是增长最快的癌症类型，谢尔曼说，难治性疾病也呈上升趋势的速率。直到近的治疗进展，从历史上看，放射性碘已提供给患者的转移性甲状腺疾病唯一的治疗方法，解释谢尔曼。虽然它确实提供了固化为一组选定的患者中，超过一半的人不给治疗的反应。

“几十年来，在这个患者人群，治疗往往是重复无效剂量的放射性碘活跃，并可能抢救治疗与化疗，”谢尔曼，这项研究的资深作者和国际首席研究员。“大约10年前，随着新型靶向药物和多靶点激酶抑制剂的日益普及，我们开始认识到潜在的用于治疗患者的这个小组有抗血管生成治疗，并寻求招收那些难治性疾病的临床试验。”

MD安德森lenvati学习的历史悠久nib, with investigators leading both Phase I and II studies. The institution was the first to study the therapy in refractory thyroid cancer patients. It also led the global Phase III trial;Mouhammed HABRA，医学博士, associate professor of Endocrine Neoplasia and Hormonal Disorders, was the institution’s principal investigator of the Phase III trial.

The international, randomized, Phase III, double-blind study enrolled 392 patients — all of whom had progressive, refractory disease — from 21 countries. Patients were randomized at a 2-1 ratio to receive either the study drug or placebo, respectively. In total, 261 received lenvatinib and 131 received a placebo. At the time of disease-progression, patients in the placebo arm could receive lenvatinib. The primary endpoint was progression-free survival; secondary endpoints tested response rate, overall survival and safety.

For those who received the study drug, the median progression-free survival rate was 18.3 months, compared with 3.6 months in those who received placebo. The overall response rate in the study arm group was 64.8% (with four complete and 165 partial responses), and 1.5% in the placebo arm. The median overall survival was not reached in either group.

For patients with advanced and metastatic disease, lenvatinib and this class of drugs is the first potential for improved overall survival.

“在我们的研究中,我们不仅看到了一个戏剧性的improvement in progression-free survival, there was also a 65 percent response rate — almost unprecedented results for thyroid cancer patients with such advanced disease. We also found a strongly suggestive trend in how long patients lived, and a small number of patients had a complete response. While we couldn’t identify tumor mutations that might predict response, this represents a very exciting area of study going forward in hopes of possibly offering cure to a greater number of patients,” says Sherman.

该药物是不是没有副作用。患者接受lenvatinib经历了一些反应，高血压是最常见的，但可以管理超过40％的谢尔曼说。其他副作用包括：腹泻，疲劳，恶心，食欲下降和重量;37例患者停药的，因为副作用的药物。此外，确定在治疗期间发生的6 20例死亡与药物相关的其治疗医生。

“The side effect profile is actually quite typical for this class of drugs. We’ve learned over the years to be aggressive about dosing modifications and coming up with clever ways of helping patients tolerate the medication where drug effectiveness is maintained but with a minimum of those side effects. It’s paramount that patients are selected carefully and physicians giving the drug focus on symptom support,” says Sherman.

A number of follow up studies with lenvatinib are in development, including in other types of thyroid cancers, and in combination with other novel therapies for radioiodine refractory patients.