NICE拒绝贝伐珠单抗+卡培他滨用于乳腺癌治疗

英格兰和威尔士的临床疗效评价机构——英国国家卫生与临床优化研究所(NICE)拒绝了第二种针对转移性乳腺癌的贝伐珠单抗联合用药方案，理由是费用较高、生活质量改善效果不确定，以及总生存率改善有力证据不足。

罗氏公司的贝伐珠单抗(阿瓦斯汀)是一种抑制血管表皮生长因子(VEGF)的单克隆抗体，欧盟已批准贝伐珠单抗联合该公司的卡培他滨(希罗达)用于治疗转移性乳腺癌，但NICE认为该联合用药方案达不到成本效益标准。自4月份NICE发布相关否决性指南草案以来，人们普遍预期该机构将会做出上述决定。

2010年，NICE拒绝贝伐珠单抗+紫杉烷类作为转移性乳腺癌一线治疗药物，而这一适应证在此前已获得批准。当年晚些时候，欧洲药品管理局(EMA)也限制了贝伐珠单抗+紫杉醇用于乳腺癌治疗。EMA于2011年4月宣布，基于来自随机、安慰剂对照RIBBON-1试验的证据，如果患者不适宜其他化疗药物，贝伐珠单抗也可与卡培他滨联合用药。该试验显示联合用药患者平均无进展生存期为8.6个月，而单纯接受卡培他滨治疗患者为5.7个月。

NICE在7月6日发布的最终评估中，认可在该项研究中合用贝伐珠单抗治疗的患者无进展生存期延长2.9个月具有统计学意义。但该机构指出，没有得到生活质量数据，而且尽管总生存期改善2.9个月，但由于部分患者接受了交叉治疗，该结果不具有统计学意义。

生产商向NICE提交的资料仅包括以前接受紫杉烷类治疗的亚组患者的临床试验证据，而完整的适用人群应包括以前曾接受治疗和从未接受治疗的患者。

NICE评审员称，没有发现以前接受治疗的亚组患者比总体患者群接受“贝伐珠单抗+卡培他滨治疗更为有效的生物学合理解释”，而后者是联合用药方案批准的适用人群。他们还指出，该联合用药增量成本-效果比至少为82,000英镑(127,000美元)/生活质量调整年(QALY)。

贝伐珠单抗静脉输注给药， 推荐剂量为10 mg/kg体重，1次/2周，或15 mg/kg体重，1次/3周。据NICE介绍，英国乳腺癌患者接受贝伐珠单抗治疗平均每月费用为3,689英镑(约合5,727美元)。

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By: JENNIE SMITH,  Oncology Report Digital Network

The clinical effectiveness agency for England and Wales has rejected a second bevacizumab combination for metastatic breast cancer, citing the treatment’s high cost, uncertain effect on quality of life, and lack of robust evidence for overall survival improvements.

Roche’s bevacizumab (Avastin) is a monoclonal antibody that works by inhibiting vascular endothelial growth factor (VEGF). It is licensed in the European Union in combination with Roche’s capecitabine (Xeloda) for metastatic breast cancer; however, the National Institute for Health and Clinical Excellence found that the treatment did not meet its cost-effectiveness criteria. NICE’s decision was widely expected after the agency issued negative draft guidance in April.

In 2010, NICE turned down bevacizumab in combination with a taxane for first-line treatment of metastatic breast cancer, its licensed indication at the time; the European Medicines Agency late that year limited the breast cancer indication to a combination with paclitaxel.

In April 2011, EMA said bevacizumab could also be used with capecitabine if other chemotherapy treatments are inappropriate, citing evidence from RIBBON-1, a randomized, placebo-controlled trial that showed average progression-free survival of 8.6 months in patients receiving the combination, compared with 5.7 months in those receiving capecitabine alone.

In a final appraisal published July 6, NICE acknowledged the statistically significant, 2.9-month gain in progression-free survival seen with bevacizumab in the trial. However, the agency said that quality-of-life data were not captured, and while median overall survival also improved by 2.9 months, this result was not statistically significant due in part to crossover.

The manufacturer’s submission to NICE included clinical trial evidence only for a subgroup of people who had been previously treated with a taxane, while the full indication includes both previously treated and treatment-naive patients.

The NICE reviewers said they found "no biologically plausible reason why bevacizumab plus capecitabine would be more effective" in the previously treated subgroup than in the broader population for which the combination is licensed. They also concluded that the incremental cost-effectiveness ratio for the treatment would be at least £82,000 (U.S.$127,000) per quality-adjusted life year (QALY).

Bevacizumab is administered by intravenous infusion at a recommended dose of 10 mg/kg of body weight once every 2 weeks or 15 mg/kg of body weight once every 3 weeks. The average price of bevacizumab treatment for breast cancer in the United Kingdom is £3,689 (U.S.$5,727) per month, according to NICE.