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Exemestane在乳癌的初步辅助治疗上优於Tamoxifen

2009-10-12 11:43:11  作者:新特药房  来源:新特药网  浏览次数:88  文字大小:【】【】【
简介: —根据发表於第15届欧洲癌症组织研讨会与第34届欧洲肿瘤医学会年会联合研讨会中的资料,使用exemestane(商品名Aromasin)辅助治疗似乎比tamoxifen更有效,更能降低乳癌病患的復发。    这项结论 .. ...
关键字: Exemestane 乳癌的

 —根据发表於第15届欧洲癌症组织研讨会与第34届欧洲肿瘤医学会年会联合研讨会中的资料,使用exemestane(商品名Aromasin)辅助治疗似乎比tamoxifen更有效,更能降低乳癌病患的復发。    
这项结论 ...(德国柏林)
—根据发表於第15届欧洲癌症组织研讨会与第34届欧洲肿瘤医学会年会联合研讨会中的资料,使用exemestane(商品名Aromasin)辅助治疗似乎比tamoxifen更有效,更能降低乳癌病患的復发。
        
这项结论来自「Tamoxifen Exemestane Adjuvant Multinational (TEAM)」研究,是比较芳香胺酶抑制剂与tamoxifen作为初步内分泌治疗效果之三个试验中最大型的研究。
        
分析显示,早期侵犯性荷尔蒙受体阳性乳癌且停经的病患,使用exemestane进行初步辅助治疗,在改善无病存活与降低疾病復发方面优於tamoxifen。
        
第一作者、荷兰Leiden大学医学中心的外科教授Cornelis van de Velde博士表示,在2.75年时,exemestane与改善无病存活、发生远端转移的时间、无復发存活等有关。
        
英国西约克夏癌症治疗研究中心临床癌症药物与肿瘤教授、临床主任Chris Twelves医师表示,此一资料相当令人印象深刻。这项研究再度提出芳香胺酶抑制剂较优,加强了我们对此类製剂的运用。
        
【TEAM试验的分析】
TEAM试验世代包括了来自9个国家、9,779名停经后且有侵犯性雌激素受体阳性和/或黄体素受体阳性的早期乳癌妇女,以前瞻性方式随机分派接受每天20mg的tamoxifen 20 mg或每天25mg的exemestane。所有病患都有完整的初步手术治疗,若适合化疗者也有接受化学治疗。
        
原始试验开始於2001年,当时的初级终点是无病存活。但是,在2004年,基於「Intergroup Exemestane Study (IES)」研究结果显示exemestane的强力利益,原始试验做了修改。所有tamoxifen组病患换成使用exemestane,期间为2.5至3年。
        
van de
Velde博士解释,修改的研究设计有两个终点。第一个比较使用tamoxifen或exemestane达2.75年之病患的无病存活。第二个比较使用exemestane 5年之妇女以及使用tamoxifen之后转用exemestane共5年之妇女的无病存活。
        
van de
Velde博士表示,目前的分析聚焦在第一个初级终点:使用tamoxifen或exemestane达2.75年之后的无病存活以及相关事件的确认。
        
结果显示,与tamoxifen相比,exemestane与较佳的无病存活有关(风险比[HR]为0.89;95%信心区间[CI]为0.77- 1.03;P= .12),无復发存活也较佳(HR,0.85%;95% CI,0.72- 1.00;P= .056)。在发生远端转移的时间方面,exemestane也较佳(HR,0.81;95% CI,0.67- 0.98;P=.028)。
        
整体而言,exemestane组的病患局部復发、远端转移、对侧乳癌、无復发的死亡案例少了11%。
        
【Tamoxifen停用率高】
在TEAM研究中,tamoxifen组停止治疗的比率(29.5%;n= 1434人)高出exemestane组(18.9%;n= 926人)许多。此外,754名使用tamoxifen的病患很早就换成exemestane。
        
van de
Velde博士表示,各国的停用率不尽相同,这一点需多加注意。我们需告知病患副作用,但是也要告诉她们持续治疗的助益。顺从性不佳也会影响芳香胺酶抑制剂试验的结果。
        
没有发生意料外的安全问题,但是使用exemestane发生关节痛、腕隧道症候群、腹泻、高胆固醇症的机会较高;两组发生心臟缺血与梗塞的比率相似。
        
【IES试验资料也显示较优的结果】
许多资料显示exemestane较优,至於在转换试验方面,英国伦敦帝国理工学院肿瘤科主任Charles Coombes博士在会议中报告了IES的长期追踪。TEAM研究设定在比较两种產品的初步治疗,IES则是比较使用tamoxifen 2到3年后转成exemestane,以及维持用tamoxifen达整整5年者。
新的长期资料证实,转换组的无病存活显著降低18% (HR,0.82;P= .0009),且显示整体存活显著延长,降低死亡风险达14% (HR,0.86;P= .04)。
        
Coombes博士在声明中表示,IES的这些新的长期追踪资料显示,转成exemestane之病患有显著的存活利益,优於那些继续使用tamoxifen者;这些发现对病患和医师一样重要,因为再度肯定使用tamoxifen2到3年后转成exemestane的信心。
        
美国和欧洲已经核准停经后且雌激素受体为阳性之早期乳癌妇女,在Tamoxifen治疗2到3年之后使用exemestane。
        
TEAM和IES研究都接受exemestane之製造商辉瑞药厂的资助。
        
第15届欧洲癌症组织研讨会(ECCO 15)与第34届欧洲肿瘤医学会年会(34th ESMO)联合研讨会:摘要 2BA (TEAM研究)与5010 (IES研究)。发表於2009年9月22日。

Exemestane Superior to Tamoxifen as Initial Adjunct Therapy in Breast
Cancer
By Roxanne Nelson
Medscape Medical News
September 29, 2009 (Berlin, Germany) — Adjuvant therapy with exemestane (Aromasin) appears to be more effective than tamoxifen in reducing disease recurrence in breast cancer patients, according to data presented here at the 15th Congress of the European CanCer Organization and the 34th European Society for Medical Oncology Multidisciplinary Congress.
The conclusions come from the Tamoxifen Exemestane Adjuvant Multinational (TEAM) study, the largest of 3 trials to compare the efficacy of an aromatase inhibitor with tamoxifen as initial endocrine therapy.
The analysis shows that in postmenopausal patients with early invasive
hormone-receptor-positive breast cancer, initial adjuvant treatment with exemestane was superior to tamoxifen in improving disease-free survival and reducing disease recurrence.
"At 2.75 years, exemestane was associated with improved disease-free survival, time to distant metastasis, and recurrence-free survival," said lead author Cornelis van?de?Velde, MD, PhD, professor of surgery at Leiden University Medical Center in the Netherlands.
"The data are very impressive," said Chris Twelves, MD, clinical director and professor of clinical cancer pharmacology and oncology at the Institute of Cancer Therapeutics in West Yorkshire, United Kingdom. "This study is another demonstration of the superiority of [aromatase inhibitors], and does reinforce that we use them up front."
Analysis of TEAM Trial
The TEAM cohort consisted of 9779 postmenopausal patients with invasive estrogen-receptor-positive and/or progesterone-receptor-positive early breast cancer from 9 countries who were prospectively randomized to tamoxifen 20?mg/day or exemestane 25?mg/day. All patients had completed primary therapy of surgery and, if indicated, chemotherapy .
The original trial began in 2001, when the primary end point was disease-free survival. But in 2004, on the basis of results of the Intergroup Exemestane Study (IES), which showed a strong benefit for exemestane, the study was amended. All patients in the tamoxifen group were switched to exemestane at 2.5 to 3 years.
The modified study design, explained Dr. van?de?Velde, had 2 end points.
The first compared disease-free survival in patients using either tamoxifen or exemestane for up to 2.75 years. The second end point compared disease-free survival in women using exemestane for 5 years with that in women using tamoxifen whoswitched to exemestane for a total of 5 years.
The current analysis focused on the first primary end point — disease-free survival after 2.75yearswithtamoxifenorexemestane — with the censoring of events, said Dr. van?de?Velde.
Their results showed that, compared with tamoxifen, exemestane is associated with better disease-free survival (hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.77?- 1.03; P?= .12) and relapse-free survival (HR, 0.85%; 95% CI, 0.72?- 1.00; P?= .056).
Time to first distant metastasis was also better with exemestane (HR, 0.81; 95% CI, 0.67?- 0.98; P?= .028).Overall, there were 11% fewer cases of local recurrence, distant metastases, contralateral breast cancer, and deaths without disease relapse for patients in the exemestane group.
Discontinuation Rates Higher for Tamoxifen In the TEAM study, a much higher rate of patients in thetamoxifengroupdiscontinued their treatment (29.5%; n?= 1434), than in the exemestane group (18.9%; n?= 926). In addition, 754 tamoxifen patients made an early switch to exemestane."Discontinuation rates varied considerably by country, and this does deserve more attention," said Dr. van?de?Velde. "We need to inform patients of the side effects, but also the benefits of continuing their treatment. Noncompliance can confound the results of [aromatase inhibitor] trials."
There were no unexpected safety issues reported, but exemestane use was associated with significantly higher incidences of arthralgia, carpal tunnel syndrome, diarrhea, and hypercholesterolemia. The incidence rate for cardiac ischemia and infarction was similar between the groups.
IES Data Also Show Superiority
More data showing superiority of exemestane, but from a switching trial, come from a long-term follow-up of the IES, and were reported at the meeting by Charles Coombes, MD, PhD, FRCP, FMedSci, head of oncology at Imperial College in London, United Kingdom.
Whereas the TEAM study set out to compare initial therapy with the 2 products, the IES comparedswitchingtoexemestane after 2 to 3 years of tamoxifen with staying on tamoxifen for the full 5 years. The new longer-term data confirm a significant 18%
reduction in disease-free survival in the group that switched (HR, 0.82; P?= .0009), and show a significant prolongation of overall survival, reducing the risk of dying by 14% (HR, 0.86; P?= .04).
"These new longer-term follow-up data from the IES demonstrate a significant survival benefit for patients who switched to exemestane compared with those who stayed on tamoxifen," Dr. Coombes said in a statement. "These findings are important to patients and physicians alike, as they reaffirm their confidence in switching to exemestane after 2 to 3 years on tamoxifen."
The use of exemestane after 2 to 3 years of tamoxifen therapy in postmenopausal women with estrogen-receptor-positive early breast cancer is an approved indication in both the United States and Europe.Both the TEAM and the IES studies were funded by Pfizer, the manufacturer of exemestane. 15th Congress of the European CanCer Organization (ECCO 15) and the 34th European Society for Medical Oncology (34th ESMO) Multidisciplinary Congress: Abstracts 2BA (TEAM study) and 5010 (IES study). Presented September 22, 2009.
      
      

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