CHMP建议批准Celgene抗癌药Abraxane用于胰腺癌治疗

美国生物制药公司新基（Celgene）11月22日宣布，抗癌药物Abraxane（紫杉醇[paclitaxel]蛋白质结合颗粒注射悬液，白蛋白结合）获得了欧洲药品管理局（EMA）人用医药产品委员会（CHMP）的积极意见。CHMP建议批准Abraxane联合吉西他滨（gemcitabine），用于转移性胰腺癌成人患者的一线治疗。

欧盟委员会（EC）预计将于2-3个月内做出最终审查决定。

CHMP的积极意见，是基于III期MPACT研究的数据。MPACT是一项开放标签、随机、国际性III期研究，研究中861例初治转移性胰腺癌患者随机接受ABRAXANE+吉西他滨联合疗法或吉西他滨单药疗法，研究数据表明，与吉西他滨单药疗法相比，ABRAXANE+吉西他滨联合疗法在总生存期（OS）、疾病无进展生存期（PFS）、整体响应率（ORR）上均表现出统计学意义的显着改善：OS（8.5个月 vs 6.7个月，HR=0.72，p＜0.0001），死亡风险降低28%；PFS（5.5个月 vs 3.7个月，HR=0.69，p＜0.0001），疾病进展或死亡风险降低31%；ORR（23% vs 7%，p＜0.0001）。

今年9月，Abraxane已获FDA批准，联合吉西他滨用于转移性胰腺癌的一线治疗。

迄今为止，吉西他滨作为胰腺癌的标准护理，已有超过15年的时间。而Abraxane+吉西他滨联合疗法，在临床试验中，已被证明对关键疗效终点表现出临床意义的显着改善，包括总生存期，同时具有良好的安全性，该联合疗法将为胰腺癌患者提供一个重要的新治疗选择，并为今后的临床研究奠定基础。

Abraxane+吉西他滨联合疗法，是近8年来获批用于转移性胰腺癌的首个新疗法。在过去的20年中，在晚期胰腺癌患者中开展了超过30项随机III期临床试验，MPACT研究便是表现出总生存期利益的4项研究之一。

关于胰腺癌：

胰腺癌是全球第8大癌症死因，在美国是第4大癌症死因。胰腺主要由2种细胞类型组成：外分泌和内分泌。外分泌肿瘤是目前最常见的一种胰腺癌，恶性腺瘤占胰腺癌症的95%。对于各个阶段的胰腺癌患者，5年的总体生存率约为6%，在美国这低于所有其他癌症的5年总体生存率。在欧洲，报告的5年生存率低于10%。

关于Abraxane：

Abraxane是紫杉醇的白蛋白结合形式，采用nab专利技术生产。Abraxane的配方中含有白蛋白，白蛋白是一种人源性蛋白质，Abraxane的配方中不含溶剂。

Abraxane于2005年1月在美国首先获准用于治疗联合化疗无效的转移性乳腺癌或辅助化疗6个月内复发的乳腺癌 。既往治疗必须包含一种蒽环类，除非有临床禁忌症。Abraxane还在下列地区获准用于治疗转移性乳腺癌：加拿大、印度、欧盟/欧洲经济区(EU/EEA)、韩国、中国、澳大利亚、不丹、阿联酋、尼泊尔、新西兰、日本、俄罗斯、斯里兰卡和阿根廷。

2012年10月，美国FDA批准Abraxane联合卡铂用于不适合治愈性手术或放疗的局部晚期或转移性非小细胞肺癌的一线治疗。此外，Abraxane也获日本和阿根廷获准用于非小细胞肺癌的治疗，并且还在日本获准用于胃癌的治疗。

Abraxane目前处于不同的研究阶段，用于下列癌症的潜在治疗：黑色素瘤、膀胱癌、卵巢癌以及乳腺癌、肺癌的扩展应用。

英文原文：Celgene Receives Positive CHMP Opinion for ABRAXANE? in Combination with Gemcitabine as Treatment for Patients with Metastatic Pancreatic Cancer

Friday, November 22, 2013 7:25 am EST

BOUDRY, Switzerland--(BUSINESS WIRE)--Celgene International Sàrl, a wholly-owned subsidiary of Celgene Corporation (NASDAQ: CELG), today announced that the European Medicines Agency’s (EMA): Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion for ABRAXANE (paclitaxel formulated as albumin bound nanoparticles, or nab-paclitaxel) in combination with gemcitabine for first-line treatment of adult patients with metastatic adenocarcinoma of the pancreas.

The CHMP reviews applications for all 28 member states in the European Union (EU), as well as Norway and Iceland. The European Commission, which generally follows the recommendation of the CHMP, is expected to make its final decision within two to three months.

The pancreas is composed of two main cell types: exocrine and endocrine. Adenocarcinoma is a sub-type of exocrine tumors and accounts for about 95% of cancers of the pancreas. Pancreatic cancer is currently the fourth most common cause of cancer death in the EU for men and women.1 Death rates from the disease are predicted to rise from 7.85 in 2009 to 8.01 in 2013 per 100,000 among men, and from 5.33 to 5.54 per 100,000 among women in same period.1 In fact, the pancreas is the only major cancer site for which no improvements in mortality rates is predicated for either sex.1 There have been no new treatments approved for pancreatic cancer in nearly seven years.

“The positive CHMP opinion on ABRAXANE with gemcitabine for metastatic pancreatic cancer is a significant step toward bringing the first new treatment option in many years to people diagnosed with this deadly disease, which has seen multiple clinical trial failures over the years,” said Alan Colowick, MD, President of Celgene Europe, the Middle East and Africa (EMEA). “Following a positive decision by the European Commission within the next few months, we hope to begin the important work of helping physicians and patients gain access to ABRAXANE plus gemcitabine, which has demonstrated statistically significant and clinically meaningful improvements in overall survival compared to gemcitabine alone, as reported recently in the New England Journal of Medicine.”

The CHMP positive opinion was based on the results of the MPACT (Metastatic Pancreatic Adenocarcinoma Clinical Trial), an open-label, phase III, randomized, international study published in the New England Journal of Medicine in its 16 October 2013 e-publication. The MPACT study involved 861 chemotherapy-na?ve patients with metastatic pancreatic cancer at 151 community and academic centers from 11 countries, including North America, Eastern and Western Europe and Australia. In the study, nab-paclitaxel plus gemcitabine demonstrated a statistically significant improvement in median overall survival compared to gemcitabine alone (8.5 vs. 6.7 months) (HR 0.72, P<0.0001); a 28% overall reduction in risk of death.2

Grade 3 and higher adverse events that were reported more often with nab-paclitaxel plus gemcitabine versus gemcitabine alone were neutropenia, leukopenia, fatigue, and peripheral neuropathy.

About ABRAXANE?

ABRAXANE is an albumin-bound form of paclitaxel that is manufactured using patented nab? technology. ABRAXANE is formulated with albumin, a human protein, and is free of solvents.

In Europe, ABRAXANE was approved in January 2008 as monotherapy for the treatment of metastatic breast cancer in adult patients who have failed first-line treatment for metastatic disease and for whom standard, anthracycline containing therapy is not indicated.

In the United States, ABRAXANE was first approved in January 2005 by the U.S. Food and Drug Administration (FDA) for the treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy. Prior therapy should have included an anthracycline unless clinically contraindicated. ABRAXANE has been globally approved in more than forty countries for the treatment of metastatic breast cancer (MBC).

In October 2012, ABRAXANE was approved by the FDA for the first-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC), in combination with carboplatin, in patients who are not candidates for curative surgery or radiation therapy. ABRAXANE is also approved for the treatment of NSCLC in Argentina, Australia, Japan, and New Zealand.

In September 2013, the FDA approved ABRAXANE as first–line treatment of patients with metastatic adenocarcinoma of the pancreas, in combination with gemcitabine.)