vicky3 2009-10-8 11:53
綜合分析結果確認Cetuximab改善NSCLC病患存活
作者：Roxanne Nelson
出處：WebMD醫學新聞
September 23, 2009（德國柏林）－根據一項收納四項隨機分派第三期研究的分析，Cetuximab（Erbitux）合併化學治療改善非小細胞肺癌（NSCLC）存活。
這項發表在第15屆歐洲癌症組織年會與第34屆歐洲內科腫瘤跨領域會議的綜合分析結果，顯示相較於僅接受化學治療的病患，接受Cetuximab加上化學治療者，其三年後續追蹤死亡的機率降低達13%。不論接受的特定化學治療療程為何，均未改變這個結果。
除此之外，接受Cetuximab的病患，疾病進展的速度較慢，且腫瘤縮小的可能性增加。
奧地利維也納醫學大學醫學教授Robert Pirker醫師表示，這項研究的結果支持Cetuximab對NSCLC是有效的觀念，強化了目前為止的證據。
Pirker醫師由Medscape接觸提供獨立評論時指出，在這個時候，cetuximab在歐洲還沒有核准使用於NSCLC。他表示，目前這個藥物大都於臨床研究中使用，即使有一些非核准適應症使用的情況。
他附帶表示，我們正在等待這個藥物獲得核准，這將為這些病患帶來好處。
過去由Medscape腫瘤學報告的研究結果，第三期FLEX研究（第一線使用Erbitux於肺癌患者研究；First-Line Erbitux in Lung Cancer）結果顯示，Cetuximab加上vinorelbine/cisplatin化學治療提供NSCLC病患一個些許的存活好處；另外三項臨床研究結果顯示，Cetuximab加上其他不同鉑金類藥物的組合。
為了確認這些研究結果的可靠性，法國Montpelier大學醫學教授、Montpelier教學醫院胸腔腫瘤科主任Jean-Louis Pujol醫師與同事們進行了一項收納四項研究的的綜合分析。
參與這四項研究的受試者總共有2,018位，Pujol醫師與其團隊收集這些病患資料，分析整體存活、免於疾病惡化存活率與客觀反應率。
Pujol醫師表示，當我們將所有族群放在一起，這項研究中就有一致性，且包括了所有病理分類。然而，這些研究中仍然有些微差異。舉例來說，四項研究中有兩項的收納標準需要抗表皮生長因子受體免疫染色陽性結果。
【所有試驗終點都看到療效】
這項綜合分析結果顯示，接受Cetuximab與其他化學治療，相較於僅接受化學治療病患，所有試驗終點都有顯著的好處。
在整體存活率，危險比值（HR）為0.87，對應為死亡風險下降13%，達到統計上顯著差異（P=0.010）。
Pujol醫師也指出，接受Cetuximab的病患，存活時間中位數顯著較高（化學治療加上Cetuximab為10.3個月，僅接受化學治療則是9.4個月）。他表示，一年時的絕對好處為5%。
其他的試驗終點也都顯示Cetuximab是有好處的。在免於疾病惡化存活率上，HR為0.899，對應為風險下降10%（P=0.038）。接受Cetuximab的病患們也有比較高的反應率，勝算比為1.463（P<0.001）。
Pujol醫師解釋，這對應為對藥物有反應的機率增加將近50%，從24%增加到36%，這達到顯著差異。
【高加索人的反應達顯著差異】
根據人種進行了一項次組分析。他指出，我們知道NSCLC隨著人種不同而有差異，因此我們認為針對高加索人的分析是很重要的，因為他們是歐洲的主要人種。
研究者們觀察到，高加索人使用Cetuximab仍然有顯著好處，且在這人種的效果甚至更大。HR為0.84，相對應於降低死亡風險16%。
接受合併化學治療與Cetuximab的高加索人種，相較於僅接受化學治療者，其預後被證實顯著較好，存活時間中位數為9.9個月，僅接受化學治療病患為8.8個月。一年時的絕對好處是6%，兩年時的絕對好處是4.5%；兩者都有顯著差異（P=0.012）。
Pujol醫師的結論是，這項綜合分析證實了Cetuximab在三種試驗終點的療效，這個好處達統計顯著差異，且在高加索人種身上甚至更有效，在一年與兩年時有顯著好處。
第15屆歐洲癌症組織年會與第34屆歐洲內科腫瘤跨領域會議：摘要9005。發表於2009年9月22日。
Cetuximab Improves Survival in NSCLC Patients, Meta-Analysis Confirms
By Roxanne Nelson
Medscape Medical News
September 23, 2009 (Berlin, Germany) — Cetuximab (Erbitux) combined with chemotherapy improves survival in patients with nonsmall-cell lung cancer (NSCLC), according to an analysis of 4 randomized phase?3 trials.
The results of the meta-analysis, which were reported here at the 15th Congress of the European CanCer Organization and the 34th European Society for Medical Oncology Multidisciplinary Congress, demonstrated that patients who received cetuximab plus chemotherapy had a 13% lower chance of dying within 3 years of follow-up, compared with those who received chemotherapy alone. This held true regardless of the specific chemotherapy regimen.
In addition, patients who received cetuximab experienced slower disease progression and an increased likelihood of tumor shrinkage.
"The results of this study support the notion that cetuximab works," in NSCLC, said Robert Pirker, MD, professor of medicine at the Medical University of Vienna in Austria. "It strengthens the evidence thus far."
Dr. Pirker, who was approached by Medscape Oncology for independent comment, pointed out that at this time, cetuximab has not yet been approved in Europe for use in NSCLC. "Right now it is used primarily in clinical trials, although there may be some off-label use," he said.
"We are awaiting its approval, and feel it will be of benefit to these patients," he added.
As previously reported by Medscape Oncology, results of the phase?3 FLEX (First-Line Erbitux in Lung Cancer) trial showed that cetuximab added to a regimen of vinorelbine/cisplatin chemotherapy offered a small survival advantage in NSCLC patients. Three other randomized trials demonstrated similar results when cetuximab was added to different platinum doublets.
To confirm the robustness of the efficacy results of these studies, Jean-Louis Pujol, MD, chair of thoracic oncology at Montpelier Academic Hospital and professor of medicine at Montpelier University in France, and colleagues conducted a meta-analysis of these 4 studies.
There were individual data for 2018 patients who participated in the 4 studies, which Dr. Pujol and his team analyzed for overall survival, progression-free survival, and objective response rate.
"When we put all of the populations together, there was consistency, and all histologies were included in this study," said Dr. Pujol.
There were, however, some slight differences in the trials, he pointed out. For example, 2 of the 4 studies required positive immunostaining against epidermal growth-factor receptor for inclusion criteria.
Efficacy Seen at All End Points
The meta-analysis demonstrated a significant benefit across all efficacy end points for patients who received cetuximab in conjunction with their chemotherapy, compared with those who did not.
For overall survival, the hazard ratio (HR) was 0.87, which corresponded to a 13% reduction in the risk for death. This was statistically significant (P?= .010).
Dr. Pujol also pointed out that patients receiving cetuximab had a longer median survival (10.3 months for chemotherapy plus cetuximab vs 9.4 months for chemotherapy alone). "The absolute benefit at 1 year was 5%," he said.
The other end points also showed a benefit for cetuximab. For progression-free survival, the HR was 0.899, corresponding to a 10% reduction in risk (P?= .038). Patients who received cetuximab also had a higher chance of being responders, with an odds ratio of 1.463 (P?< .001).
"This corresponds to an almost 50% greater chance of being a responder," explained Dr. Pujol. The increase rose "from 24% to 36%, and that was highly significant."
Response in Caucasians Significant
A subanalysis was conducted on the basis of ethnicity. "We know that NSCLC behaves differently according to ethnicity, so we felt it was important to look at a subgroup of Caucasians, as they are the prominent ethnic group in Europe," he said.
The researchers observed that there was a statistically significant benefit favoring cetuximab among Caucasians, and it had a more pronounced effect in this group. The HR of 0.84 corresponded to a risk for death of 16%.
Caucasian patients who received combination chemotherapy plus cetuximab proved to have a better prognosis than those who didn't, with a median survival of 9.9 months, compared with 8.8 months for those who didn't. The absolute benefit at 1 year was 6%, and the absolute benefit at 2 years was 4.5%. Both were significant (P?= .012).
"This meta-analysis confirms the efficacy of cetuximab for the 3 end points, and the benefit is statistically significant and is more pronounced in the Caucasian population," Dr. Pujol concluded, "with a striking benefit at 1 and 2 years."
15th Congress of the European CanCer Organization (ECCO 15) and the 34th European Society for Medical Oncology (34th ESMO) Multidisciplinary Congress: Abstract 9005. Presented September 22, 2009.