Dunn Christopher, Keam Susan J
Adis International Limited, Mairangi Bay, Auckland, New Zealand.
Pharmacoeconomics. 2006;24(5):495-517. doi: 10.2165/00019053-200624050-00007.
Letrozole (Femara), an aromatase inhibitor that blocks estrogen synthesis by inhibiting the final step of the estrogen biosynthetic pathway, is approved for use in a wide range of breast cancer settings. Randomised clinical trials in postmenopausal women with hormone-responsive early-stage breast cancer have demonstrated that, as adjuvant therapy, letrozole has greater efficacy than tamoxifen. It is also more effective than placebo as extended adjuvant therapy after completion of tamoxifen therapy in these patients. In women with hormone-responsive advanced breast cancer, letrozole is superior to tamoxifen in prolonging the time to disease progression and time to treatment failure in a first-line setting, and is at least as effective as anastrozole and more effective than megestrol for some endpoints (in one of two trials) in a second-line setting. Letrozole is generally well tolerated, and in a health-related quality-of-life analysis from a large clinical trial, patient well-being with letrozole as extended adjuvant therapy did not differ from that with placebo. Modelled analyses from the UK and the US suggest that, in postmenopausal women with hormone-receptor-positive early-stage breast cancer, letrozole is likely to be a cost-effective alternative to tamoxifen as adjuvant therapy; moreover, using letrozole as extended adjuvant therapy after tamoxifen, rather than no further treatment, is also a cost-effective treatment strategy. Sensitivity analyses have shown these results to be robust. In terms of direct healthcare costs, pharmacoeconomic models suggest that letrozole is a cost-effective alternative to tamoxifen as first-line therapy in postmenopausal women with hormone-responsive advanced breast cancer from the perspectives of the UK NHS, the Canadian and Italian public healthcare systems and the Japanese national health insurance system. Incremental costs per QALY or progression-free year gained over tamoxifen were well within the recommended limits for acceptability of new agents that are more effective and more expensive than existing therapies in the UK, Japan and Canada. Modelled analyses from the UK and Canada have also suggested that letrozole is cost effective as second-line therapy for advanced breast cancer in postmenopausal women who have disease progression following anti-estrogen therapy. In conclusion, letrozole is an effective and well tolerated treatment for postmenopausal women with early-stage or advanced hormone-responsive breast cancer. Pharmacoeconomic analyses from UK and North American perspectives support the use of letrozole in hormone-responsive early-stage breast cancer in both the adjuvant and extended adjuvant settings. In addition, other modelled analyses conducted in a variety of healthcare systems across different countries consistently suggest that letrozole is cost effective in advanced treatment settings.
来曲唑（芙瑞）是一种芳香化酶抑制剂，通过抑制雌激素生物合成途径的最后一步来阻断雌激素合成，已被批准用于多种乳腺癌治疗场景。针对激素反应性早期乳腺癌的绝经后女性进行的随机临床试验表明，作为辅助治疗，来曲唑的疗效优于他莫昔芬。在这些患者完成他莫昔芬治疗后作为延长辅助治疗，来曲唑也比安慰剂更有效。在激素反应性晚期乳腺癌女性中，一线治疗时来曲唑在延长疾病进展时间和治疗失败时间方面优于他莫昔芬，二线治疗时在某些终点（两项试验中的一项）至少与阿那曲唑疗效相当且比甲地孕酮更有效。来曲唑一般耐受性良好，在一项大型临床试验的健康相关生活质量分析中，来曲唑作为延长辅助治疗时患者的幸福感与安慰剂组无异。英国和美国的模型分析表明，对于激素受体阳性的绝经后早期乳腺癌女性，来曲唑作为辅助治疗可能是比他莫昔芬更具成本效益的选择；此外，在他莫昔芬治疗后将来曲唑作为延长辅助治疗，而非不再进行进一步治疗，也是一种具有成本效益的治疗策略。敏感性分析表明这些结果是可靠的。在直接医疗成本方面，药物经济学模型表明，从英国国民健康服务体系、加拿大和意大利公共医疗系统以及日本国家医疗保险系统的角度来看，来曲唑作为激素反应性晚期乳腺癌绝经后女性的一线治疗药物，是比他莫昔芬更具成本效益的选择。与他莫昔芬相比，每获得一个质量调整生命年（QALY）或无进展年的增量成本完全在英国、日本和加拿大对于比现有疗法更有效且更昂贵的新药物可接受性的推荐范围内。英国和加拿大的模型分析还表明，对于抗雌激素治疗后疾病进展的绝经后晚期乳腺癌女性，来曲唑作为二线治疗具有成本效益。总之，来曲唑是治疗绝经后早期或晚期激素反应性乳腺癌的有效且耐受性良好的药物。从英国和北美的角度进行的药物经济学分析支持在辅助和延长辅助治疗环境中使用来曲唑治疗激素反应性早期乳腺癌。此外，在不同国家的各种医疗系统中进行的其他模型分析一致表明，来曲唑在晚期治疗环境中具有成本效益。
