ST LOUIS (MD Consult) - On August 2, 2009, Genentech announced that the US Food and Drug Administration (FDA) had approved Avastin (bevacizumab) in combination with interferon-α for the treatment of metastatic renal cell carcinoma (RCC), the most common type of kidney cancer. Avastin has been previously approved for the treatment of various other types of cancer.

Avastin specifically binds to the vascular endothelial growth factor (VEGF) protein, a protein produced in elevated amounts in most cases of kidney cancer. This protein is thought to be a key component in cancer growth because it plays an important role throughout the lifecycle of a tumor through the process of angiogenesis. Avastin is designed to interfere with the blood supply to a tumor by directly binding to the VEGF protein to prevent interactions with receptors on blood vessel cells. Avastin does not bind to receptors on normal or malignant cells. A tumor's blood supply is thought to be critical in promoting tumor growth and cancer spread.

The FDA approval of Avastin for this indication was granted on the basis of data from a global, randomized, double-blind, placebo-controlled, phase 3 study of 649 patients with previously untreated metastatic RCC. Study results demonstrated that patients who received Avastin plus interferon-α sustained a 67% increase in progression-free survival (PFS) compared with patients who received interferon-α alone (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.49-0.72). In this study, the median PFS was 10.2 months for patients who received Avastin plus interferon-α compared with 5.4 months for patients who received interferon-α alone, corresponding to an 89% improvement in median PFS.

Secondary analysis end points of the study included objective response rate and overall survival (OS). The results showed a tumor size decrease of 30% in patients in the Avastin plus interferon-α group, compared with a 12% decrease in patients in the interferon-α plus placebo group. No improvement in OS was appreciated on final data analysis after 444 deaths occurred, with a median OS of 23 months in the Avastin plus interferon-α arm and 21 months in the interferon-α plus placebo arm (HR, 0.86; 95% CI, 0.72-1.04).

 

Adverse events in this study were consistent with those previously reported for Avastin or interferon-α. The most common severe (grade 3-5) adverse events that occurred at a rate of at least 2% more often in patients who received Avastin plus interferon-α versus interferon-α plus placebo included fatigue (13% vs 8%), weakness (10% vs 7%), proteinuria (7% vs 0%), hypertension (6% vs 1%), and bleeding (3% vs 0.3%).

 

圣路易斯(MD Consult)——2009年8月，基因泰克公司宣布，美国食品药品管理局(FDA)已批准阿瓦斯汀(贝伐单抗)联合干扰素α用于治疗转移性肾细胞瘤(RCC)——最常见的肾癌类型。阿瓦斯汀先前已获准作为其他各型癌症的治疗药。

 

阿瓦斯汀可特异性地与血管内皮细胞生长因子(VEGF)蛋白(在大多数肾癌患者中生成量增加的一种蛋白)相结合。此蛋白因其在血管新生过程中乃至整个肿瘤生命周期中起着重要作用，故被视为癌生长的关键要素。阿瓦斯汀通过直接与VEGF蛋白结合防止其与血管细胞上的受体相互作用，干扰肿瘤的血供；此药并不与正常细胞及恶性细胞上的受体相结合。据认为，肿瘤的血供对促进肿瘤生长和癌症扩散非常重要。

FDA批准阿瓦斯汀这一新适应证是基于一项全球性、随机、双盲、安慰剂对照、3期临床研究的数据，该研究共纳入649例患有转移性RCC但未经治疗的患者。研究结果证实，接受阿瓦斯汀加干扰素α治疗的患者无进展生存期(PFS)较仅接受干扰素α治疗者增加67%(HR，0.60；95% CI，0.49~0.72)。在这项研究中，接受阿瓦斯汀加干扰素α治疗的患者中位PFS为10.2个月，而仅接受干扰素α治疗者为5.4个月，相当于前者中位PFS增加5.4个月。

此研究的次要分析终点包括客观有效率和总生存期(OS)。结果显示，阿瓦斯汀加干扰素α治疗组瘤体缩小30%，而干扰素α加安慰剂对照组患者缩小12%。在444例患者死亡后做最终数据分析时发现，阿瓦斯汀加干扰素α治疗组中位OS为23个月，而干扰素α加安慰剂对照组为21个月，相比之下，前者的OS无增加(HR，0.86；95% CI，0.72~1.04)。

这项研究中的不良事件与此前针对阿瓦斯汀或干扰素α报告的不良事件一致。最常见的严重(3~5级)不良事件包括疲劳(13% 比 8%)、虚弱(10%比7%)、蛋白尿(7% 比 0%)、高血压(6% 比1%)和出血(3%比 0.3%)，与接受干扰素α加安慰剂对照处置的患者相比，上述事件在接受阿瓦斯汀加干扰素α治疗者中的发生率至少高2%。