Citing high costs and uncertain overall survival benefit, the clinical effectiveness agency for England and Wales said Dec. 8 it would not recommend bevacizumab in combination with taxane chemotherapy for the treatment of metastatic breast cancer.

The decision by the National Institute for Health and Clinical Excellence comes ahead of the U.S. Food and Drug administration’s decision on whether to change or revoke the breast-cancer indication for bevacizumab. The FDA’s decision is expected Dec. 18.

The European Medicines Agency has also been reviewing bevacizumab. The EMA will decide whether to change, leave in place, or suspend the drug’s marketing authorization for breast cancer in the face of what it has described as an inconsistent evidence base.

Bevacizumab is a humanized monoclonal antibody, delivered by intravenous infusion. It works by reducing the vascularization of tumors and is administered in combination with chemotherapy drugs. Evidence that was initially submitted by bevacizumab’s manufacturer to NICE was based on one open-label clinical trial (n = 722) comparing bevacizumab plus paclitaxel vs. paclitaxel alone. Progression-free survival was 11.3 months in the bevacizumab arm, compared with 5.8 months for the paclitaxel-alone arm. But median overall survival was improved by only 1.7 months in the bevacizumab arm (26.5 vs. 24.8 months), and these results did not reach statistical significance.

After earlier negative draft guidance in July, bevacizumab’s manufacturer submitted to NICE the results from a randomized, double-blind trial of bevacizumab that was combined with a different taxane chemotherapy drug, docetaxel. This trial (n = 736) looked at the combination of bevacizumab with docetaxel in women with HER2-negative disease who had not previously received chemotherapy for metastatic disease. Patients received either docetaxel plus bevacizumab at 7.5 mg/kg every 3 weeks, docetaxel plus bevacizumab at 15 mg/kg every 3 weeks, or docetaxel alone.

The trial showed a 2-month, statistically significant improvement in progression-free survival for bevacizumab and docetaxel at the higher dose, compared with docetaxel alone. However, bevacizumab’s overall survival benefit again proved elusive, with slightly longer median overall survival seen in the docetaxel-alone arm than in the bevacizumab arms (31.9 vs. 30.2 months).

Finally, the manufacturer presented to NICE evidence for subgroups of breast cancer patients who had previously received treatment with a taxane or who had breast cancer that was negative for the estrogen and progesterone receptor along with HER2. However, NICE was not persuaded that bevacizumab would be any more effective in either patient group.

Nor was NICE inclined to forgive bevacizumab’s high price relative to its benefits. Bevacizumab is administered at 10 mg/kg of body weight and is given once every 2 weeks (or 15 mg/kg once every 3 weeks). The average costs per patient for bevacizumab plus paclitaxel are estimated at £33,649; NICE estimated that the costs per quality-adjusted life-year gained would be £115,000-£259,000 for metastatic breast cancer treatment involving bevacizumab, depending on the chemotherapy drug used. The appeal period for the appraisal ends Jan. 4, after which final guidance will be issued.

Also on Dec. 8, NICE said that a court decision had forced it to reconsider its guidance on of strontium ranelate, a medication that is used to prevent bone fractures in postmenopausal women with osteoporosis. The drug’s manufacturer contended that NICE’s cost-benefit analysis for the drug – which NICE recommends to certain patients only – was opaque and needed to be revised. Strontium ranelate is currently recommended by NICE for this patient group, but only as a last resort if three other drugs cannot be tolerated or are contraindicated.

The dispute was over evidence from a post hoc study that was accepted by the European Medicines Agency in support of strontium ranelate’s marketing authorization. The EMA accepted that the drug decreased hip fractures by 36%; NICE’s own analysis had resulted in an estimated 15% decrease. The agency will issue new guidance on strontium ranelate “in due course,” it said.

Copyright (c) 2010 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

英国国家卫生与临床优化研究所(NICE) 12月8日宣布，基于高成本和总体生存受益不确定性，该机构将不推荐贝伐单抗(bevacizumab)联合紫杉烷类化疗用于转移性乳腺癌治疗。 

贝伐单抗是一种人源化单克隆抗体，可抑制肿瘤血管生成，与化疗药物联合用于乳腺癌治疗。贝伐单抗制造商最初向NICE提交的证据是一项开放性贝伐单抗加紫杉醇与单纯紫杉醇对比临床试验(n = 722)结果，但因贝伐单抗组中位总体生存时间仅比单纯紫杉醇组延长1.7个月 (26.5对 24.8 个月)，没有统计学意义，NICE在7月份公布的贝伐单抗使用指南草案中，不推荐贝伐单抗量紫杉醇用于转移性乳腺癌治疗。 

指南草案公布之后，制造商向NICE提交了一项随机、双盲贝伐单抗试验结果。该试验(n = 736)是将贝伐单抗与另一种紫杉烷化疗药物多西他赛联合用药，用于无化疗史的HER2阴性转移性乳腺癌女性患者，患者接受多西他赛+贝伐单抗(7.5 mg/kg 或15 mg/kg，每3周1次)或单纯多西他赛治疗。结果显示，与单纯多西他赛组相比，高剂量贝伐单抗+多西他赛组无进展生存期有统计学显著改善，但中位总体生存时间仅略有延长(31.9 对 30.2个月)，仍未见总体生存受益。最后，制造商又向NICE提交了有紫杉烷类化疗史的乳腺癌患者或有雌、孕激素受体以及HER2阴性的乳腺癌患者亚组的有关试验证据。然而，NICE认为贝伐单抗并对上述两组患者并没有更好的疗效。 

除患者受益之外，NICE对其昂贵价格也不认同。贝伐单抗给药方案为10 mg/kg体重，1次/2周(或15 mg/kg体重， 1次/3周)，毎例患者贝伐单抗加紫杉醇的平均费用约为33,649英镑。NICE估计贝伐单抗治疗转移性乳腺癌，依据所用化疗药物的不同，每延长1个质量调整生命年所需费用为115,000~259,000英镑。 

NICE评估的申诉截止日期为1月4日，届时最终指南将予以公布。美国FDA预计在12月18日做出有关是否改变或撤销贝伐单抗用于乳腺癌治疗的决定。欧洲药品管理局(EMA)也已经启动对贝伐单抗的复审，也将做出是否改变、保留或暂停该药物用于乳腺癌治疗的上市许可。 

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