4月18日,，《美國醫(yī)學(xué)會(huì)雜志》（Journal of American Medical Association）上的一項(xiàng)研究披露,，對(duì)美國食品和藥物管理局（FDA）在2006年批準(zhǔn)的一個(gè)治療非小細(xì)胞肺癌的藥物治療方案（將貝伐單抗添加到卡鉑和紫杉醇的標(biāo)準(zhǔn)化療方案中）的分析發(fā)現(xiàn),，擁有醫(yī)療保險(xiǎn)的接受這一療法的年齡在65歲及以上的病人與那些僅接受標(biāo)準(zhǔn)的卡鉑和紫杉醇治療者相比,，他們的存活率并沒有改善；這是一期有關(guān)對(duì)比性效益研究的?？?。
根據(jù)文章的背景資料：“一項(xiàng)先前的隨機(jī)性的試驗(yàn)顯示，將貝伐單抗添加到卡鉑和紫杉醇中可改善晚期非小細(xì)胞肺癌（NSCLC）患者的存活率,。但是,，在那些年齡為65歲及以上的病人亞組中則沒有觀察到較長(zhǎng)的存活率。”
波士頓Dana-Farber癌癥研究所的Deborah Schrag, M.D., M.P.H.及其同事們開展了一項(xiàng)研究,，旨在檢查將貝伐單抗添加到卡鉑-紫杉醇中是否與醫(yī)療保險(xiǎn)人群的存活率的改善有關(guān),。研究人員應(yīng)用分析策略來解決因缺乏在觀察性研究中的治療隨機(jī)化造成的混淆性（即那些會(huì)影響結(jié)果的因子）和選擇性的偏差，觀察性研究中的治療隨機(jī)化的缺乏會(huì)限制對(duì)因果關(guān)系做出有效推論的能力,。這一研究包括了4,168名年齡為65歲或以上的罹患晚期（IIIB期或IV期）非鱗狀細(xì)胞NSCLC的醫(yī)療保險(xiǎn)受益人,，他們是在2002-2007年間被診斷的。患者根據(jù)診斷的年份及在診斷后的4個(gè)月中所給予的最初化療的類型被分為三個(gè)群組：(1) 在2006-2007做出診斷并給予貝伐單抗-卡鉑-紫杉醇療法,；(2) 在2006-2007做出診斷并給予卡鉑-紫杉醇療法,；或 (3) 在2002-2005做出診斷并給予卡鉑-紫杉醇療法。研究人員用不同的模型和方法對(duì)卡鉑-紫杉醇加上貝伐單抗 vs. 卡鉑-紫杉醇不加貝伐單抗與總體存活率之間的關(guān)系進(jìn)行了比較,。
研究人員發(fā)現(xiàn),， 在2006-2007年間，接受貝伐單抗組合療法的患者的總體存活率中位數(shù)（中點(diǎn)）為9.7個(gè)月,，而那些接受卡鉑-紫杉醇療法的患者的總體存活率中位數(shù)為8.9個(gè)月,；在2002-2005年間，那些接受卡鉑-紫杉醇療法的患者的總體存活率中位數(shù)則為8.0個(gè)月,。在2006-2007年間,，貝伐單抗-卡鉑-紫杉醇組患者中的1年存活概率為39.6% vs.卡鉑-紫杉醇組患者中的40.1% 及 2002-2005年間在卡鉑-紫杉醇組患者中的35.6%。在對(duì)人口和臨床特點(diǎn)進(jìn)行控制的校正過的模型中,，在2006-2007年間或在2002-2005年間,，文章的作者在接受貝伐單抗治療的病人與那些僅接受卡鉑-紫杉醇治療的病人中沒有發(fā)現(xiàn)其總體存活率之間存在有明顯的差異。
文章的作者得出結(jié)論：“將來,，對(duì)像NSCLC這樣不成比例地影響老年患者的惡性腫瘤或由美國醫(yī)療保險(xiǎn)和醫(yī)療救助服務(wù)中心（CMS）支付絕大部分治療成本的惡性腫瘤,，與制藥贊助商進(jìn)行的關(guān)鍵性試驗(yàn)的談判可能會(huì)命令性要求有足夠的老年患者的代表性及/或與預(yù)先計(jì)劃的和醫(yī)療投保人群有關(guān)的亞組分析。如果沒有這一信息,，臨床醫(yī)生將需要依靠來自隨機(jī)性試驗(yàn)的亞組分析的療效數(shù)據(jù),、像本報(bào)告這樣的觀測(cè)數(shù)據(jù)及他們的臨床判斷來做出治療的建議。鑒于來自功效研究的亞組分析或觀測(cè)數(shù)據(jù)分析都沒有發(fā)現(xiàn)在標(biāo)準(zhǔn)的卡鉑-紫杉醇治療中添加貝伐單抗的益處,；因此,，在這種情況下，貝伐單抗不應(yīng)被考慮作為標(biāo)準(zhǔn)的治療,。臨床醫(yī)生在作出治療建議的時(shí)候應(yīng)該謹(jǐn)慎并應(yīng)在他們的老年患者中審慎地使用貝伐單抗,。”（生物谷Bioon.com）
doi:10.1001/jama.2012.454
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Carboplatin and Paclitaxel With vs Without Bevacizumab in Older Patients With Advanced Non–Small Cell Lung Cancer
Junya Zhu, MS, MA; Dhruv B. Sharma, PhD; Stacy W. Gray, MD, AM; Aileen B. Chen, MD, MPP; Jane C. Weeks, MD, MS; Deborah Schrag, MD, MPH
Abstract
Context A previous randomized trial demonstrated that adding bevacizumab to carboplatin and paclitaxel improved survival in advanced non–small cell lung cancer (NSCLC). However, longer survival was not observed in the subgroup of patients aged 65 years or older.
Objective To examine whether adding bevacizumab to carboplatin and paclitaxel chemotherapy is associated with improved survival in older patients with NSCLC.
Design, Setting, and Participants Retrospective cohort study of 4168 Medicare beneficiaries aged 65 years or older with stage IIIB or stage IV non?squamous cell NSCLC diagnosed in 2002-2007 in a Surveillance, Epidemiology, and End Results (SEER) region. Patients were categorized into 3 cohorts based on diagnosis year and type of initial chemotherapy administered within 4 months of diagnosis: (1) diagnosis in 2006-2007 and bevacizumab-carboplatin-paclitaxel therapy; (2) diagnosis in 2006-2007 and carboplatin-paclitaxel therapy; or (3) diagnosis in 2002-2005 and carboplatin-paclitaxel therapy. The associations between carboplatin-paclitaxel with vs without bevacizumab and overall survival were compared using Cox proportional hazards models and propensity score analyses including information about patient characteristics recorded in SEER-Medicare.
Main Outcome Measure Overall survival measured from the first date of chemotherapy treatment until death or the censoring date of December 31, 2009.
Results The median survival estimates were 9.7 (interquartile range [IQR], 4.4-18.6) months for bevacizumab-carboplatin-paclitaxel, 8.9 (IQR, 3.5-19.3) months for carboplatin-paclitaxel in 2006-2007, and 8.0 (IQR, 3.7-17.2) months for carboplatin-paclitaxel in 2002-2005. One-year survival probabilities were 39.6% (95% CI, 34.6%-45.4%) for bevacizumab-carboplatin-paclitaxel vs 40.1% (95% CI, 37.4%-43.0%) for carboplatin-paclitaxel in 2006-2007 and 35.6% (95% CI, 33.8%-37.5%) for carboplatin-paclitaxel in 2002-2005. Neither multivariable nor propensity score–adjusted Cox models demonstrated a survival advantage for bevacizumab-carboplatin-paclitaxel compared with carboplatin-paclitaxel cohorts. In propensity score–stratified models, the hazard ratio for overall survival for bevacizumab-carboplatin-paclitaxel compared with carboplatin-paclitaxel in 2006-2007 was 1.01 (95% CI, 0.89-1.16; P = .85) and compared with carboplatin-paclitaxel in 2002-2005 was 0.93 (95% CI, 0.83-1.06; P = .28). The propensity score–weighted model and propensity score–matching model similarly failed to demonstrate a statistically significant superiority for bevacizumab-carboplatin-paclitaxel. Subgroup and sensitivity analyses for key variables did not change these findings.
Conclusion Adding bevacizumab to carboplatin and paclitaxel chemotherapy was not associated with better survival among Medicare patients with advanced NSCLC.
