本帖最後由 lsc0019 於 2009-4-18 10:52 編輯
作者：Zosia Chustecka
出處：WebMD醫學新聞
April 2, 2009 — 美國食品藥物管理局（FDA）腫瘤藥物顧問委員會（ODAC）快速核准了Bevacizumab（Avastin，Genentech／羅氏藥廠）用於過去曾接受過治療的神經母細胞瘤病患。FDA預計在5月5日對這個核准案做出決議。
北卡羅萊納州杜克大學醫學教授James Vrendenberg博士向Medscape腫瘤學表示，這項核准案的投票結果是全體一致的，與會的10位委員全數通過，他期待FDA會同意這個核准案。他指出，Bevacizumab已經被美國許多地方的臨床醫師使用於治療神經母細胞瘤，因為這是個有急迫醫療需求的狀況，且沒有更好有益的治療方法。
這將會是這個藥物的另一個適應症。Bevacizumab，是一種血管內皮生長因子（VEGF）的單株抗體，這個藥物已經被核准用於大腸直腸癌、肺臟與乳癌。
Vrendenberg博士也參與ODAC會議，他是被討論到的臨床研究研究者之一，且是製造廠商的顧問之一。
會中發表的臨床研究數據是來自一項第二期臨床研究，這項研究並沒有對照組，但是其研究結果明顯比歷史控制組好，反應率是過去從未見到的四倍。Vrendenberg博士表示，過去的研究曾經針對irinotecan、lomustine、etoposide與其他藥物進行研究。反應率的定義是間隔四週連續兩次獨立的評估，腫瘤大小至少縮小50%。
他進一步表示，所有數據都指向有好處的方向。六個月免於惡化的存活率、整體存活率、以及停止使用類固醇的比例都比歷史控制組好，所以這是個有明顯好處的事情。
這項研究名為BRAIN，針對167位過去曾接受治療的神經母細胞瘤病患，當這個研究在設計時，我們覺得納入可能治療無效的比較組是不道德的。那組將只使用irinotecan，但過去已經有許多報告指出bevacizumab對這個病患族群是有效的。因此，這項研究提供病患bevacizumab（共85位病患）或是bevacizumab合併irinotecan。
這些病患過去曾接受放射線與temozolomide（Temodar，先靈葆雅藥廠），這是新診斷神經母細胞瘤的確立標準治療。另外兩項研究正在探索加上bevacizumab是否會改善預後。這兩項研究都是第三期臨床研究，結果預計在2014年發表。
Vrendenberg博士評論，bevacizumab是腦部腫瘤疾病的一個重要發展，利用母細胞瘤的生物學來更有效地治療這種疾病。
他解釋，母細胞瘤非常依賴VEGF，所以這是除了腎細胞惡性腫瘤之外，一個預期VEGF抑制劑將會有效，且其他治療可能不會那麼有效的藥物。這是我們已經發現的，只是花了很長的時間來檢驗其療效。
不過，他也表示，這只是個開端，還有許多令人興奮的臨床研究正在進行，而腦瘤患者有希望改善他們的存活率。
Vrendenberg博士在Genentech／羅氏藥廠擔任顧問。
Bevacizumab in Glioblastoma Approval Recommended
By Zosia Chustecka
Medscape Medical News
April 2, 2009 — Bevacizumab (Avastin, Genentech/Roche) has been recommended for accelerated approval for use in patients with previously treated glioblastoma by the US Food and Drug Administration (FDA) Oncologic Drugs Advisory Committee (ODAC). The FDA is expected to make a decision about the approval by May 5.
The vote for recommending approval was unanimous, with all 10 members agreeing, James Vrendenberg, MD, professor of medicine at Duke University, in Durham, North Carolina, told Medscape Oncology. He expects that the FDA will grant this approval. Bevacizumab is already being used by many clinicians in the United States for previously treated glioblastoma, because this is a setting of urgent medical need in which there are no other beneficial therapies, he said.
This will be an additional indication for the product. Bevacizumab, a monoclonal antibody inhibitor of vascular endothelial growth factor (VEGF), is already approved for use in colorectal, lung, and breast cancer
Dr. Vrendenberg was present at the ODAC meeting as 1 of the investigators of the clinical trial that was being discussed and as a consultant for the manufacturers.
The clinical data presented at the meeting came from a phase?2 trial that had no comparator group, but the results were significantly better than have been seen with historic controls, and the response rate was 4 times higher "than has ever been seen," Dr. Vrendenberg noted. Previous studies have investigated irinotecan, lomustine, etoposide, and other drugs, he said. The response rate was defined as a decrease in tumor size by at least 50% on 2 consecutive independent assessments at least 4 weeks apart.
"All the data went in the same direction of benefit," he continued. The results for 6-month progression-free survival, overall survival, and discontinuation of steroids were all significantly better than historic controls, so there was a "clear story of benefit," he added.
The study, known as BRAIN, was conducted in 167 patients with previously treated glioblastoma and, "when it was being designed, we felt it was immoral to have a comparator arm that would be ineffective," Dr. Vrendenberg said. That group would have been irinotecan alone, but there had already been several studies suggesting that bevacizumab is effective in this patient population. Hence, the study offered patients either bevacizumab alone (n?= 85 patients) or bevacizumab in combination with irinotecan.
These patients had previously been treated with radiation and temozolomide (Temodar, Schering-Plough), which is the established standard therapy for newly diagnosed glioblastoma. This is the setting in which 2 new trials are exploring whether the addition of bevacizumab can improve outcomes. Both are phase?3 trials, with results expected in about 2014.
"Bevacizumab is a major step for the brain tumor community, and takes advantage of glioma biology to treat it more effectively," Dr. Vrendenberg commented.
Gliomas are very dependent on VEGF, he explained. "So this is the 1 tumor — in addition to renal cell carcinoma — in which you would predict that VEGF inhibitors would work well and other treatments would not work well. And that's what we have found; it has just taken a long time to test it."
"I also think this is just the beginning," he added. "There are some very exciting clinical trials and there is hope for better survival for brain tumor patients."
Dr. Vrendenberg acts as a consultant to Genentech/Roche. |
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