The clinical effectiveness agency for England and Wales said that it will not recommend erlotinib for the maintenance treatment of non–small cell lung cancer, citing the drug’s high cost.

In November 2008, the National Institute for Health and Clinical Excellence recommended erlotinib (Tarceva, Roche), which works by inhibiting the epidermal growth factor receptor tyrosine kinase, as a second-line treatment option for people with advanced or metastatic NSCLC.

But the agency said in draft guidance issued June 16 that it could not recommended erlotinib as a maintenance treatment option for NSCLC, though the drug had been shown to prolong overall and progression-free survival when used in maintenance therapy after a platinum-based chemotherapy.

The NICE reviewers evaluated data from a manufacturer-sponsored randomized controlled trial (n = 889) of erlotinib as a maintenance therapy in NSCLC patients (J. Clin. Oncol. 27:15s, 2009 [suppl; abstr 8001]). They questioned whether the trial had adequate blinding; whether the trial’s findings could be generalized to the United Kingdom because some of the first-line and postprogression treatments used among the study patients were different than those standard in U.K. practice; and the fact that the study patients were generally younger (mean age 60) than patients presenting in the United Kingdom, and 21% of the study patients were Southeast Asian (though nearly half were Eastern European).

Despite these caveats, the agency’s modeled estimates of overall survival gain with erlotinib maintenance, 4.2 months, in fact exceeded those provided to NICE by the manufacturer, which had estimated 3.3 months.

Still, the agency said, the costs of maintenance therapy with erlotinib, for people with stable disease who have already undergone first-line treatment with a platinum-based therapy, were too steep.

Erlotinib’s manufacturer, Roche, had offered to discount the drug by 14.5% to the National Health Service, allowing it to buy each pack of 30 tablets (150 mg each) for £1,394.96, instead of the listed £1,631.53. But NICE said that its best-case estimate of £59,300 per quality-adjusted life-year gained still made erlotinib maintenance too expensive for the benefits.

The guidance is not final until July 27; the agency is accepting comments until July 7.

Erlotinib is one of several agents currently being appraised by NICE alone or in combination as maintenance therapies for people with NSCLC. In April, the agency issued draft guidance recommending pemetrexed (Alimta, Eli Lilly), a chemotherapy drug that works by inhibiting RNA and DNA production, as a maintenance treatment option for people in the same patient group with predominantly squamous cell histology. NICE’s final word on pemetrexed is expected this month.

The agency is also evaluating erlotinib in combination with bevacizumab, (Avastin, Genentech/Roche), a vascular endothelial growth factor inhibitor, as a potential maintenance therapy for NSCLC patients who have already undergone first-line treatment with a platinum-based therapy.

Currently there is no maintenance therapy, aside from best supportive care, recommended by NICE for this patient group.

Copyright (c) 2009 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

英格兰和威尔士临床疗效评价机构宣称，考虑到厄洛替尼价格昂贵，该机构将不会推荐应用该药对非小细胞肺癌(NSCLC)患者进行维持治疗。

 

2008年11月，英国国家卫生与临床优化研究所(NICE)推荐将厄洛替尼(Tarceva，罗氏公司)作为治疗晚期或转移性NSCLC患者的二线治疗药物，该药主要通过抑制表皮生长因子受体酪氨酸激酶而发挥作用。

 

但该机构在6月16日发布的指南草案中指出，其不推荐应用厄洛替尼对NSCLC患者进行维持治疗，尽管研究业已证明，患者在接受以铂类药物为主的化疗后应用该药进行维持治疗可以延长患者的总体和无进展生存期。

 

NICE评审专家对一项由制造商赞助的、旨在评估厄洛替尼作为NSCLC患者维持治疗药物的随机对照临床试验(n = 889)的数据进行了评估(J. Clin. Oncol. 27:15s, 2009 [suppl; abstr 8001])。他们对该试验是否完全符合盲法的要求以及该试验的结果能否在全英国范围内推广表示怀疑，其原因在于，在该研究中，患者应用的某些一线治疗方案及病情进展后的治疗方案有别于英国临床实践中所应用标准方案，此外，与在英国的此类患者相比，该研究的受试者普遍更加年轻(平均年龄60岁)，且其中有21%是东南亚人(尽管其中有近乎一半受试者是东欧人)。

 

尽管存在上述这些不足，据该机构应用模型预测的结果显示，应用厄洛替尼进行维持治疗的患者总体生存期延长了4.2个月，实际上这一数值比制造商提供给NICE的数值(据制造商估计，该数值为3.3个月)更高。

 

然而，该机构还宣称，对于那些之前接受过以铂类药物为主的一线治疗方案且疾病处于稳定期的患者而言，应用厄洛替尼进行维持治疗的花费太高了。

 

厄洛替尼的制造商罗氏公司已经主动提出在为英国国家卫生服务体系(NHS)提供该药物时降价14.5%，这就使得患者购买每包药(含有30片该药物，每片150 mg)的价格从1,631.53英镑下降至1,394.96英镑。但NICE称，据其估计，即便在最佳情况下，患者每延长1个质量调整生命年也需要花费59,300英镑，就厄洛替尼维持治疗为患者带来的收益而言，其花费太高昂了。

 

该指南的最终发布日期是6月27日，该机构接受评议的截止日期是6月7日。

 

厄洛替尼是NICE目前作为NSCLC患者维持治疗药物进行单独或联合评估的数种药物之一。该机构在4月发布的指南草案中推荐使用培美曲赛(力比泰，礼来公司)作为组织学类型以鳞状细胞为主的同类患者的维持治疗药物，该药通过抑制RNA和DNA合成而发挥作用。NICE关于培美曲赛的最终结论预期将于本月发布。

 

该机构目前还在对联合应用厄洛替尼与贝伐单抗(Avastin，基因泰克/罗氏)进行评估，后者是一种血管内皮生长因子抑制剂，对已接受以铂类药物为主的一线治疗的NSCLC患者而言，该药还是一种潜在的维持治疗药物。

 

目前，除了最佳支持治疗外，NICE并未为这一患者群体推荐其他任何维持治疗药物。

 

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