研究回顧衡量Trastuzumab用於乳癌的利益與風險


  【24drs.com】根據線上發表於考科藍實證醫學資料庫的系統性回顧,Trastuzumab顯著改善早期與局部惡化乳癌HER2陽性婦女的整體存活及無病存活;不過,它也顯著增加了心臟問題的風險。
  
  義大利米蘭大學Lorenzo Moja醫師表示,因此,醫師們必須和每個病患討論心血管風險並且衡量藥物的可能利益。
  
  Moja醫師表示,就是為了平衡利益與風險。對醫師而言,最重要的是確認服用trastuzumab的病患是否有心血管毒性高風險。舉凡高血壓、家庭或個人有心衰竭病史、心肌梗塞都是警訊,對這些病患來說,或許就不能像其他沒有風險的病患那樣使用trastuzumab。
  
  Moja醫師表示,已經確認trastuzumab對早期和局部惡化HER2陽性乳癌有效,但是它的實際效益與相關的心臟毒性則未被充分探討。因此他們希望探究支持trastuzumab之效益和安全性的證據,以幫助醫師和病患更明智地衡量風險與利益。
  
  研究者搜尋了Cochrane Breast Cancer Group Specialised Trials Register,確認8篇隨機控制試驗,包括11,991名HER2陽性、可開刀的乳癌婦女,包括局部惡化乳癌者。
  
  這些隨機控制試驗檢視了只有使用trastuzumab、併用trastuzumab和化療、無治療、單用標準化療的效果與安全性,這些婦女被追蹤平均3年。
  
  回顧發現,使用trastuzumab治療的婦女,其乳癌死亡率降低了三分之一(風險比[HR]0.66;95%信心區間[CI]0.57-0.77;P< .00001)。Trastuzumab也顯著降低了無病存活率(HR,0.60;95% CI,0.50- 0.71;P< .00001)。
  
  不過,與單用標準治療者相比,服用trastuzumab的婦女,鬱血性心衰竭風險增加5倍,使用trastuzumab的鬱血性心衰竭風險為5.11 (90% CI,3.00- 8.72;P< .00001),左心室射出分率衰減的相關風險為1.83 (90% CI,1.36 - 2.47;P= .0008)。
  
  Moja醫師表示,如果1,000名婦女給予標準治療但未使用trastuzumab,3年後有900例存活、5例發生心臟毒性;如果1,000名婦女使用標準化療和trastuzumab 1年,約933人存活,所以,用trastuzumab治療1,000名婦女,多了33人可以延長存活。
  
  不過,每1,000名使用trastuzumab治療的婦女,有26人會有嚴重心臟毒性,比單用化療組多出21人;心臟毒性風險隨婦女原本的風險因素而增加,所以,必須與病患討論風險及利益之間的平衡。
  
  紐約James P. Wilmot癌症中心的Alissa Huston醫師表示,這篇統合分析增加證據顯示,trastuzumab對HER2陽性乳癌病患之整體和無病存活提供效益,特別是那些高風險疾病者。
  
  Huston醫師表示,確實曾經發現過心臟毒性,此次分析加以強調,顯示任何治療務必要衡量利益與風險的重要性,特別是有潛在心臟風險因素或者更易發病者。她指出,Trastuzumab依舊是HER2陽性乳癌病患最重要且有效的療法。
  
  資料來源:http://www.24drs.com/professional/list/content.asp?x_idno=6793&x_classno=0&x_chkdelpoint=Y

Review Weighs Trastuzumab's Benefits and Risks in Breast Cancer

By Fran Lowry
Medscape Medical News

April 17, 2012 — Trastuzumab significantly improves overall and disease-free survival in HER2-positive women with early and locally advanced breast cancer, according to a systematic review published online today in Cochrane Database of Systematic Reviews. However, it also significantly increases their risk for heart problems.

For this reason, doctors need to discuss the cardiovascular risk with each of their patients and weigh the drug's potential benefits, lead author Lorenzo Moja, MD, from the University of Milan in Italy, told Medscape Medical News.

"It's all about balance. The most important thing is for doctors to determine whether the patient has a high risk for developing cardiotoxicity with trastuzumab. Hypertension, a family or personal history of heart failure, and myocardial infarctions are all warning signs. For these patients, trastuzumab may not be indicated as much as it would be for other patients with no risk," Dr. Moja said.

It has already been established that trastuzumab is of benefit for early and locally advanced HER2-positive breast cancer, but its net benefit and associated cardiotoxicity has not been fully addressed, Dr. Moja said.

Accordingly, he and his group set out to assess the evidence supporting the efficacy and safety of trastuzumab to help clinicians and their patients more intelligently weigh its risks and benefits.

The researchers searched the Cochrane Breast Cancer Group Specialised Trials Register and identified 8 randomized controlled trials involving 11,991 women with HER2-positive operable breast cancer, including women with locally advanced breast cancer.

The randomized controlled trials examined the efficacy and safety of trastuzumab alone, trastuzumab in combination with chemotherapy, no treatment, and standard chemotherapy alone. The women were followed for an average of 3 years.

The review found that overall, breast cancer mortality was reduced by one third in the women treated with trastuzumab (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.57 to 0.77; P < .00001).

Disease-free survival was also significantly reduced with trastuzumab (HR, 0.60; 95% CI, 0.50 to 0.71; P < .00001).

However, the risk for congestive heart failure rose 5-fold in women receiving trastuzumab, compared with those receiving standard therapy alone. The relative risk for congestive heart failure with trastuzumab was 5.11 (90% CI, 3.00 to 8.72; P < .00001). The relative risk for left ventricular ejection fraction decline was 1.83 (90% CI, 1.36 to 2.47; P = .0008).

"If 1000 women were given standard therapy with no trastuzumab, 900 would survive and 5 would have experienced heart toxicities after 3 years. If 1000 women were treated with standard chemotherapy and trastuzumab for a year, about 933 would survive, so for every 1000 women treated with trastuzumab, 33 more will have their lives prolonged," Dr. Moja said.

However, "for every 1000 women treated with trastuzumab, 26 would have serious heart toxicity, 21 more than the chemotherapy-alone group. The risk for cardiotoxicity increases as the woman's baseline risk increases, so the balance between risk and benefit must be discussed with the patient," he explained.

Trastuzumab Remains an Important Treatment

This meta-analysis adds to the data showing that trastuzumab provides a benefit for both overall and disease-free survival in patients with HER2-positive breast cancer, particularly those with high-risk disease, Alissa Huston, MD, from the James P. Wilmot Cancer Center in Rochester, New York, told Medscape Medical News.

"The cardiac toxicity that has been observed, and which is highlighted in the analysis, underscores the importance of always weighing the risks and benefits of any treatment, particularly in patients who have underlying cardiac risk factors and who may be more susceptible," Dr. Huston said.

"Trastuzumab remains an important and extremely effective treatment for patients with HER2-positive breast cancer," she added.

This study was funded by the Italian Medicines Agency (Agenzia Italiana del Farmaco). Dr. Moja and Dr. Huston have disclosed no relevant financial relationships.

Cochrane Database Syst Rev.2012;4:CD006243.

    
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