作者：Nick Mulcahy
出處：WebMD醫學新聞
October 17, 2008 — 參與無症狀轉移荷爾蒙難治前列腺癌的第3期免疫治療臨床試驗的Cell Genesys公司宣布，因為缺乏存活效果而終止；該試驗於2007年共募集了626名病患，比較GVAX免疫治療和docetaxel (Taxotere，Sanofi-Aventis公司)化療加prednisone的效果。
Cell Genesys主席暨執行長Stephen A. Sherwin醫師在記者會中表示，我並未對免疫治療將在此疾病中扮演某種角色失去信心，有許多臨床前與初步臨床資料顯示GVAX的活性，因此我依舊樂觀。
在思索試驗的失敗過程中，Sherwin醫師表示，轉移前列腺癌即使比其他癌症較無侵犯性，用來作為GVAX這種緩慢作用的免疫治療的目標還是太強。
Sherwin醫師也認為，是否公司把第3期試驗的目標訂得太高，把GVAX視為一種活性化療藥物。
該公司根據此一研究的獨立資料監控委員會(IDMC)進行的計畫外無用分析結果，終止這項試驗，委員會指出符合預期的存活改善終點不到30%。
該治療的另一個第3期試驗VITAL-2，在2008年8月27日終止，現在，GVAX免疫治療的VITAL-1第3期臨床試驗也終止了。
相較於VITAL-1研究，VITAL-2研究的對象是有症狀的轉移荷爾蒙難治前列腺癌，比較併用GVAX免疫治療加docetaxel與docetaxel加prednisone(控制組)的效果。
當VITAL-2 研究終止時，IDMC報告指出，在該委員會的常規安全監控會議中觀察發現，兩個治療組之間的死亡件數差異很大。IDMC當時回顧的114名死亡案例中，67人發生在接受GVAX 免疫治療加docetaxel這一組，47人發生在接受docetaxel加prednisone這組；當時總共有408名病患納入試驗。
Cell Genesys公司現在進行不完整的VITAL-2資料庫的初步分析，由IDMC在8月進行回顧，Sherwin醫師在記者會中提供更新的資料；該分析發現，就病患的人口統計與疾病預後因素來看，該分析沒有失衡。此外，GVAX 免疫治療加docetaxel並未出現可以解釋造成死亡失衡的顯著毒性。兩個治療組的大部份死亡原因是前列腺癌惡化。
Sherwin醫師表示，明顯地，接受GVAX 免疫治療的病患，其docetaxel治療循環，比併用prednisone者少，這個差異有統計上的顯著意義。
GVAX 免疫治療，前列腺癌病患門診真皮內注射，包括兩個前列腺腫瘤細胞線，修飾為分泌顆粒性巨噬細胞株刺激因子(GM-CSF)，這是一種免疫刺激細胞激素，在身體的免疫反應扮演刺激的角色，與安全有關。Sherwin 醫師形容GM-CSF是一種強力細胞激素，指出它因為活性，在各種免疫治療試驗中都作為輔助治療。
Cell Genesys公司暫緩GVAX免疫治療用於前列腺癌的進一步發展，直到該計畫的合作藥廠Takeda Pharmaceutical公司完成回顧為止。
Sherwin醫師在記者會中感謝參與試驗的病患，身為Cell Genesys公司管理團隊的代表，我要對參加這項研究的勇敢病患表達深摯的感激，也感謝臨床試驗研究者及其團隊。
根據Sherwin醫師表示，因為終止這項臨床試驗，Cell Genesys公司將在年底將290名員工減少75%，2009年上半年將會有進一步的裁員，因為後續活動也逐步停止。
Phase 3 Trial of Immunotherapy for Metastatic Prostate Cancer Terminated
By Nick Mulcahy
Medscape Medical News
October 17, 2008 — A phase?3 clinical trial of an immunotherapy in patients with asymptomatic metastatic hormone-refractory prostate cancer has been terminated by its corporate sponsor, Cell Genesys, Inc, of South San Francisco, California, because of a lack of effect on survival, the company announced.
The trial was fully enrolled in 2007 with 626 patients and compared GVAX immunotherapy with docetaxel (Taxotere, Sanofi-Aventis) chemotherapy plus prednisone.
"I have not lost my conviction that immunotherapy will play a role in the treatment of this disease," said Stephen A. Sherwin, MD, chair and chief executive officer of Cell Genesys, in a press conference call with reporters. "There's a huge amount of preclinical and early clinical data suggesting the activity of this platform [GVAX ], and that's why I remain optimistic."
In speculating about the failure of trial, Dr. Sherwin said: "Perhaps metastatic prostate cancer, even though it's less aggressive than other cancers, is simply just too tough a target for a slow-acting immunotherapy such as GVAX."
Dr. Sherwin also wondered if the company had "raised the bar too high in these phase?3 trials when we put GVAX up against an active chemotherapy drug."
The company ended the trial based on the results of an unplanned futility analysis conducted by the study's Independent Data Monitoring Committee (IDMC), which indicated that the trial had less than a 30% chance of meeting its prespecified primary end point of an improvement in survival.
The termination of the VITAL-1 phase?3 clinical trial of GVAX immunotherapy follows the termination, on August 27, 2008, of VITAL-2, another phase?3 trial involving the therapy.
In contrast to the VITAL-1 study, the VITAL-2 study was conducted in patients with symptomatic metastatic hormone-refractory prostate cancer and compared the combination of GVAX immunotherapy plus docetaxel to docetaxel plus prednisone (the control group).
When the VITAL-2 study was terminated, the IDMC reported an imbalance in deaths between the 2 treatment groups that was observed during a routine safety-monitoring meeting of the committee. Of 114 deaths at the time of the IDMC review, 67 occurred in the group receiving GVAX immunotherapy plus docetaxel, and 47 occurred in the group receiving docetaxel plus prednisone. A total of 408 patients had been enrolled in the study up to that point.
Cell Genesys has now conducted an initial analysis of the incomplete VITAL-2 dataset that was reviewed by the IDMC in August, and Dr. Sherwin provided an update during the press conference. The analysis has revealed no imbalance in patient baseline characteristics with respect to demographic and disease prognostic factors. In addition, no significant toxicities were observed with GVAX immunotherapy plus docetaxel that could explain the imbalance in deaths. The vast majority of deaths in both treatment groups were reported as being due to the progression of prostate cancer.
Notably, fewer treatment cycles with docetaxel were administered to patients receiving GVAX immunotherapy than to those receiving prednisone, said Dr. Sherwin, and the difference was statistically significant.
GVAX immunotherapy, an intradermal injection administered on an outpatient basis for prostate cancer, is comprised of 2 prostate tumor cell lines that have been modified to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF), an immune-stimulatory cytokine that plays a key role in stimulating the body's immune response, and then irradiated for safety. Dr. Sherwin called GM-CSF a "powerful cytokine," and noted that it is used "across the board in immunotherapy trials as an adjunctive therapy" because of its potency.
Cell Genesys has put on hold the further development of GVAX immunotherapy for prostate cancer pending a review of the program with its collaborator, Takeda Pharmaceutical Co. Ltd.
Dr. Sherwin thanked the patients in the study during his press conference. "On behalf of the Cell Genesys management team, I would like to express my deep gratitude to the courageous patients who participated in this study, as well as to our committed clinical-trial investigators and their teams."
As a result of the terminated clinical trials, Cell Genesys will reduce its staff of 290 by approximately 75% by year-end, with further reductions anticipated in the first half of 2009 as additional activities are phased out, according to Dr. Sherwin.
[ 本帖最後由 goodcat1111 於 2008-10-27 13:14 編輯 ] |
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