The clinical effectiveness agency for England and Wales says that it will not recommend two cancer drugs, one to treat a bone cancer primarily affecting young people and another to treat metastatic breast cancer, citing limited data and high costs.

The National Institute for Health and Clinical Excellence, in draft guidance issued July 9, said that mifamurtide, an immune macrophage stimulant is not recommended to treat high-grade non-metastatic osteosarcoma in people younger than 30 because of inadequate survival data.

NICE based its efficacy analysis on one, 678-subject randomized trial comparing mifamurtide (Mepact, Takeda) in combination with two different chemotherapy regimens to the same regimens without mifamurtide.

Though the mifamurtide-containing regimens were shown to prolong overall survival (78% in the mifamurtide arm over 8 years, compared with 71% in the control arm), the trial data pooled the mifamurtide-containing regimens and did not compare them individually, NICE reviewers noted. And improvements in disease-free survival, the primary endpoint of the trial, were not shown to be statistically significant, despite the trial’s power to detect them, the agency said.

The NICE guidance on osteosarcoma currently recommends treatment with doxorubicin, methotrexate and cisplatin, and the 5-year overall survival rate for patients treated in the United Kingdom has remained approximately 55% for two decades, the agency said. Ultimately the cost of mifamurtide, at £114,000 for a full treatment course of 48 intravenous doses, proved too much for NICE, even with the manufacturer’s offer to pick up the cost of the first 7 doses.

Also on July 9 NICE issued draft guidance against the use of bevacizumab in combination with a taxane (paclitaxel or docetaxel) for the first-line treatment of metastatic breast cancer.

Bevacizumab (Avastin, Roche) is a humanized monoclonal antibody that inhibits vascular endothelial growth factor, reducing blood flow to tumors; the drug is delivered intravenously.

In the sole randomized controlled trial (n=722) presented by the manufacturer and assessed by NICE reviewers, people receiving bevacizumab and paclitaxel saw median progression-free survival of 11.3 months, compared with 5.8 months in the paclitaxel alone arm. However, median overall survival was increased by only 1.7 months, from 24.8 with paclitaxel alone to 26.5 with bevacizumab and paclitaxel. NICE criticized the trial’s lack of blinding and found the 1.7 month survival benefit inadequate to justify the drug’s cost. Also, the agency said no clinical evidence of the effectiveness of bevacizumab plus docetaxel had been presented despite published data (J Clin. Oncol, 2008; 26 [May 20 suppl; abstr LBA1011]) from a trial comparing bevacizumab plus docetaxel with docetaxel alone. The results of that trial (n=736) showed a 2-month improvement in progression-free survival for bevacizumab at 15 mg/m² plus docetaxel over docetaxel alone.

Though NICE’s cost estimates per quality-of-life adjusted year gained varied wildly for treatment with bevacizumab plus paclitaxel, the lowest-cost scenario proposed was approximately £118,000 per QALY.

For both drugs, mifamurtide and bevacizumab, final guidance will not be issued until mid-August; the deadline for comments is July 30.

 

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)在发表于6月9日的指南草案中说，米伐木肽作为一种巨噬细胞免疫兴奋剂，因生存数据不充分，故不推荐用于治疗年龄不足30岁的高分化非转移性骨肉瘤患者。

 

NICE的疗效分析是基于一项包括678例受试者的随机试验，该试验将两种不同的化疗方案联合米伐木肽(Mepact，武田制药)治疗与同一化疗方案不联合米伐木肽治疗进行比较。

 

该研究显示，含有米伐木肽的治疗方案可延长总生存时间(米伐木肽亚组有78%的患者生存时间超过8年，而对照组有71%)，但试验数据汇总的是含有米伐木肽治疗方案的数据，且未对其进行一 一比较，NICE评审员指出。该试验的主要终点——无病生存状况——的改善并不具有统计学意义，尽管试验的效能足以对其进行检测，NICE指出。

 

NICE骨肉瘤诊治指南目前推荐使用多柔比星、甲氨蝶呤及顺铂进行治疗，在英国接受此治疗方案的患者5年总生存率在20年中一直保持在接近55%的水平，NICE说。一个完整的米伐木肽疗程包括48剂静脉用药，其最终治疗费用达114,000英镑，NICE认为即便生产厂家为前7剂埋单，米伐木肽的治疗费用仍过于昂贵。

 

NICE在6月9日发布的指南草案中还反对以贝伐单抗联用紫杉醇类药物(紫杉醇或多西紫杉醇)作为转移性乳腺癌的一线治疗方案。

 

贝伐单抗(商品名Avastin，罗氏公司生产)是一种人源性单克隆抗体，可抑制血管内皮生长因子，减少肿瘤的血供；该药为静脉用药。

 

在由生产厂家提供、由NICE评估的惟一一项随机对照试验(n=722例患者)中，接受贝伐单抗配伍紫杉醇治疗的患者中位无进展生存时间为11.3个月，而紫杉醇单药治疗组为5.8个月。中位总生存时间仅增加1.7个月：紫杉醇单药治疗组为24.8个月，贝伐单抗配伍紫杉醇治疗组为26.5个月。NICE批评该试验未使用盲法，并发现这1.7个月的生存收益不足以支持该药的昂贵费用。同时NICE称，尽管生产厂家发表了一项贝伐单抗加多西紫杉醇与多西紫杉醇单药治疗比较试验的数据，但未提供贝伐单抗加多西紫杉醇治疗有效的临床证据。此试验结果表明，15 mg/m²贝伐单抗加多西紫杉醇治疗组无进展生存时间较多西紫杉醇单药治疗组增加2个月。

 

尽管对于贝伐单抗加紫杉醇治疗，NICE估算的每获得一个质量调整生命年(QALY)的费用存在很大差异，但是，所提议的最低费用约为118,000英镑/QALY。

 

有关米伐木肽和贝伐单抗这两种抗癌药的最终指南将在8月中旬出台；征求意见截止日期为6月30日。

 

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