FDA批准Abraxane新适应证——晚期胰腺癌

美国食品药品管理局（FDA）9月6日宣布批准Abraxane——白蛋白结合型紫杉醇联合吉西他滨用于转移性胰腺癌的一线治疗。

根据FDA的声明，批准微管蛋白抑制剂Abraxane（紫杉醇蛋白结合注射悬浊液，白蛋白结合型）的这一新适应证是基于一项相关研究的结果。该研究显示，与单用吉西他滨治疗的患者相比，使用Abraxane联合吉西他滨治疗的患者生存期和无进展生存期延长了近2个月（中位数）。

FDA药品评价与研究中心血液科和肿瘤科产品办公室主任Richard Pazdur医生在声明中说，多数胰腺癌患者在确诊时已到晚期且无法行手术治疗，“或在术后癌症发生了进展，此时采用Abraxane这类治疗方案可以帮助延长患者的生命”。

这项国际性研究以861例转移性胰腺癌患者为研究对象，比较了以Abraxane+吉西他滨与以吉西他滨单药治疗作为一线治疗方案的患者结局。这些患者的中位年龄是63岁，其中近半数有≥3处转移（84%有肝转移）。

使用联合疗法的患者中位生存期是8.5个月，而单用吉西他滨治疗者则是6.7个月，具有显著的统计学差异；使用联合疗法的患者中位肿瘤无进展生存期为5.5个月，而单用吉西他滨者为3.7个月，也具有显著的统计学差异。另外，根据处方信息，联合治疗组有23%的患者获得明确的完全或部分应答，而单用吉西他滨治疗组仅有7%。

根据赛尔基因公司的声明，这项名为IMPACT（转移性胰腺癌临床试验）的研究结果已提交发表，并将在今年的美国临床肿瘤学会(ASCO)年会上展示。

与Abraxane+吉西滨他联合疗法有关的常见不良事件有中性粒细胞减少、血小板减少、周围神经病变、恶心、脱发、周围水肿、腹泻、发热、呕吐、皮疹和脱水。发热、脱水、肺炎和呕吐是最常见的严重不良事件。据FDA称，其他“临床上重要的”不良事件包括脓毒病和肺炎。

根据胰腺癌治疗的新处方信息，Abraxane（125 mg/m²）的1个疗程为28天，在每个疗程的第1、8、15天经静脉给药，随后立即序贯应用吉西他滨。根据FDA在声明中援引国家癌症研究所的估计数据，胰腺癌在美国癌症死亡原因中位列第四， 2013年预计有45,220人被诊断为胰腺癌，38,460人将死于此病。

Abraxane由赛尔基因公司经销，在2005年获准用于治疗乳腺癌，2012年获准用于治疗小细胞肺癌。吉西他滨是一种核苷代谢抑制剂，商品名为健择（Gemzar），由礼来制药公司经销，在1996年通过批准，现也有仿制药可供选用，并且吉西他滨现已获准用作胰腺癌单药治疗。

可登录以下网址查阅修订后的说明书：www.accessdata.fda.gov/drugsatfda_docs/label/2013/021660s037lbl.pdf。

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By: ELIZABETH MECHCATIE, Internal Medicine News Digital Network

The albumin-bound formulation of paclitaxel has been approved by the Food and Drug Administration as a first-line treatment for metastatic adenocarcinoma of the pancreas, in combination with gemcitabine, the agency announced on Sept. 6.

The expanded indication for Abraxane (paclitaxel protein-bound particles for injectable suspension, albumin-bound), a microtubule inhibitor, is based on a study that found survival and progression-free survival were a median of almost 2 months longer among those treated with Abraxane and gemcitabine, compared with those treated with gemcitabine alone, according to the FDA statement announcing the approval.

When pancreatic cancer is diagnosed in an advanced stage and is inoperable, which is often when pancreatic cancer is diagnosed, "and in situations when the cancer has progressed following surgery, options like Abraxane can help prolong a patient’s life," Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in the statement.

The international study compared Abraxane plus gemcitabine with gemcitabine alone as a first-line treatment in 861 people with metastatic adenocarcinoma of the pancreas. Their median age was 63 years, and almost half had three or more sites of metastasis (84% had liver metastases).

Median overall survival was 8.5 months in those on the combination vs. 6.7 months among those on gemcitabine alone, a highly statistically significant difference. Median progression-free survival was 5.5 months among those on the combination vs. 3.7 months for those on gemcitabine alone, also a highly statistically significant difference. In addition, 23% of those in the combination arm had a confirmed complete or partial overall response, compared with 7% of those on gemcitabine, according to the prescribing information.

The results of the study, IMPACT (Metastatic Pancreatic Adenocarcinoma Clinical Trial), have been submitted for publication, according to the Celgene statement announcing the approval, and were presented at the American Society of Clinical Oncology annual meeting this year.

Common adverse events associated with treatment with Abraxane and gemcitabine included neutropenia, thrombocytopenia, peripheral neuropathy, nausea, alopecia, peripheral edema, diarrhea, fever, vomiting, rash, and dehydration. Fever, dehydration, pneumonia, and vomiting were the most common serious adverse events. Other "clinically important" adverse events included sepsis and pneumonitis, according to the FDA.

According to the new prescribing information, for pancreatic cancer, Abraxane (125 mg/m2) is administered intravenously on days 1, 8, and 15 of each 28-day cycle, followed by gemcitabine immediately afterwards. In the United States, pancreatic cancer is the fourth-leading cause of cancer deaths, according to the FDA statement, which cites National Cancer Institute estimates that 45,220 patients will be diagnosed with pancreatic cancer and 38,460 will die from the disease in 2013.

Abraxane, marketed by Celgene, was approved for treating breast cancer in 2005 and non–small cell lung cancer in 2012. Gemcitabine, a nucleoside metabolic inhibitor marketed as Gemzar by Eli Lilly, was approved in 1996 and is also available in generic formulations. Gemcitabine is approved as a single agent to treat pancreatic cancer.

The revised label is available at www.accessdata.fda.gov/drugsatfda_docs/label/2013/021660s037lbl.pdf.