The clinical effectiveness agency for England and Wales has reversed earlier negative guidance on trastuzumab for metastatic gastric cancer and now recommends that the drug be available through the National Health Service, albeit to a more narrowly defined group of patients than its licensed indication covers.

The National Institute for Health and Clinical Excellence said September 29 that trastuzumab (Herceptin, Roche) should be made available to people with metastatic gastric cancer whose tumors express very high levels of human epidermal growth factor receptor 2 (HER-2), and who have not received prior treatment for their metastatic disease. Trastuzumab, a humanized monoclonal antibody, targets HER-2 and is licensed in combination with cisplatin and either capecitabine or 5-fluorouracil for patients with HER-2-overexpressing metastatic adenocarcinoma of the stomach or gastroesophageal junction who have not received prior treatment.

Trastuzumab is already recommended by NICE for the treatment of breast cancers that overexpress HER-2.

One randomized manufacturer-sponsored trial (n=594) compared trastuzumab plus cisplatin and either capecitabine or 5-fluorouracil in this patient group with a double chemotherapy regimen using a platinum agent and a fluoropyrimidine (J. Clin. Oncol. 27:18s, 2009 [suppl; abstr LBA4509]). The results showed improved overall survival in the treatment arm (a median 13.8 months compared with 11.1 months in the chemotherapy arm).

In a subgroup of people whose tumors expressed high levels of HER-2 (n=446), median survival for the trastuzumab plus chemotherapy arm was 16 months compared with 11.8 months for the chemotherapy alone group, a 4.2 month improvement.

In December 2009, the European Medicines Agency recommended a marketing authorization for trastuzumab to treat the same gastric cancer patients included in the trial subgroup with high HER-2 expression. These patients were defined as having an immunohistochemistry 2 (ICH2) positive result for HER-2 confirmed by a fluorescence in situ hybridization (FISH) positive result, or an IHC3 positive result without further confirmation. Herceptin was granted marketing authorization (an extension of indication) in Europe by the European Commission for gastric cancer in February 2010.

But the NICE guidance, which will not be made final until November, would allow only patients with the highest HER-2 expression – represented by an IHC3 positive result -- to have access to the medication. Approximately 8,200 people are diagnosed with gastric cancer in the United Kingdom every year. Of these, approximately 500 are HER-2 positive, about 300 of whom express high levels of HER2 as defined by a IHC3 positive result, NICE said.

In July, NICE had issued preliminary guidance against trastuzumab for metastatic gastric cancer, earning itself the ire of physician and patient groups that considered the medication – the first biological agent licensed for gastric cancer -- a breakthrough for a type of cancer that has seen very little in the way of treatment advances for the past decade.

NICE had complained then that trastuzumab’s demonstrated survival benefit against a double regimen of a platinum agent and a fluoropyrimidine therapy (that is, capecitabine or 5-fluorouracil) could not be compared to standard U.K. clinical practice, usually a triple therapy of these agents plus an anthracycline. NICE also argued that trastuzumab’s cost-effectiveness was unclear, compared with standard triple chemotherapy, and that at an estimated £67,000 or more per quality-of-life-adjusted year gained, it was too expensive.

Trastuzumab’s manufacturer, Roche Products, responded to the negative appraisal with new data from the same trial based on a subgroup of people who tested IHC 3 positive (n =2 79), expressing the highest amount of HER-2. In this subgroup, the survival benefits in the treatment arm (n = 144) were even greater: 18 months compared with 12.4 months for the chemotherapy alone group, a 5.6 month improvement.

This data helped persuade NICE that trastuzumab was cost-effective in this patient group, bringing down cost estimates to between £45,000 and £50,000 per quality-of-life-adjusted year gained.

Trastuzumab costs £407.40 per 150-mg vial. It is administered by intravenous infusion in a loading dose of 8 mg per kilogram of body weight, followed by 6 mg/kg 3 weeks later and then 6 mg/kg repeated at three weekly intervals. The total treatment cost of trastuzumab is approximately £10,185 per patient based on a patient weight of 62 kg, NICE 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）修订了原有有关使用曲妥珠单抗的诊疗指南，即不在转移性胃癌患者中应用该药。新指南建议在国民保健服务体系内可应用该药物，但是适用患者群较其核准上市的适应人群窄。

 

NICE宣布，自9月29日曲妥珠单抗（赫赛丁，罗氏公司）可用于治疗高表达人表皮生长因子受体2 (HER-2)且未接受其他抗转移治疗的转移性胃癌患者。不过，诊疗指南最终版本要在12月完成。曲妥珠单抗是靶向HER-2的人单克隆抗体，批准用于与顺铂和卡培他滨或5-氟脲嘧啶联合治疗HER-2过表达的未接受过其他治疗的转移性胃或食管胃交界处的腺癌。

 

2009年12月，欧洲药品管理局给予曲妥珠单抗治疗HER-2高表达的胃癌患者的上市授权。患者需具备以下条件：HER-2免疫组织化学（ICH）染色2+，并经荧光原位杂交（FISH）确认阳性结果；或HER-2的ICH染色3+，无需进一步确认。欧盟委员会则在2010年2月批准赫赛丁作为治疗胃癌的药物上市销售。

 

但NICE诊疗指南中要求只有HER-2的IHC染色3+的患者才可用药。

 

现有研究结果显示，将曲妥珠单抗联合化疗药物应用于HER-2的ICH染色3+患者，与单纯应用化疗相比，可将生存期提高5.6个月。该研究数据使曲妥珠单抗在此类患者中达到了NICE的费用-效益要求。

 

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