PAI (Policy Analysis Inc.), Brookline, MA 02445, USA.
Curr Med Res Opin. 2010 Oct;26(10):2315-28. doi: 10.1185/03007995.2010.510784.
The Breast International Group (BIG) 1-98 and Arimidex, Tamoxifen Alone or in Combination (ATAC) trials demonstrated that, in postmenopausal women with hormone receptor positive (HR+) early-stage breast cancer, 5 years of initial adjuvant endocrine therapy with letrozole or anastrozole is superior to tamoxifen. With expected generic availability of anastrozole in July 2010 and letrozole in June 2011, there may be financial pressures prior to letrozole's generic availability to start treatment-naïve patients on anastrozole vs. letrozole or to switch patients already receiving letrozole to anastrozole.
A Markov model was used to estimate cost per quality-adjusted life-year (QALY) gained with letrozole vs. anastrozole from the US healthcare system perspective. Cost effectiveness was examined separately in treatment-naïve patients and in patients already receiving letrozole. For the latter, cost effectiveness of continued letrozole vs. therapeutic substitution (TS) to generic anastrozole was evaluated separately in cohorts defined on years of endocrine therapy remaining. TS to generic anastrozole was assumed to result in an additional 5% of patients discontinuing endocrine therapy. Probabilities of distant recurrence and death were taken from reports of BIG 1-98, ATAC, the Early Breast Cancer Trialists' Collaborative Group meta-analysis of tamoxifen, and other published sources. Carry-over effects of aromatase inhibitors were assumed to be proportional to treatment duration. Costs of aromatase inhibitors were assumed to decline by 75% with generic availability.
In treatment-naïve patients, total expected lifetime costs are $3916 greater with letrozole vs. anastrozole. However, initiation of treatment with letrozole results in a gain of 0.15 QALYs. Cost per QALY gained with letrozole vs. anastrozole is $25,846. In patients already receiving letrozole, the increase in total expected lifetime costs with continued letrozole vs. TS to anastrozole is between $4200 and $4500 in all cohorts. QALYs gained with letrozole range from 0.21 in those with 4 years of endocrine therapy remaining to 0.13 in those with 1 year of therapy remaining. Cost per QALY gained ranges from $20,276 to $34,356.
For postmenopausal women with HR+ early-stage breast cancer, letrozole is more likely to be cost effective vs. anastrozole in treatment-naïve patients and in patients already receiving letrozole. Limitations of the study include a lack of direct evidence comparing letrozole and anastrozole and lack of data on rates of discontinuation due to therapeutic substitution with aromatase inhibitors.
乳腺国际集团（BIG）1-98 号试验和阿那曲唑、他莫昔芬单独或联合应用（ATAC）试验表明，对于绝经后激素受体阳性（HR+）早期乳腺癌患者，5 年初始辅助内分泌治疗使用来曲唑或阿那曲唑优于他莫昔芬。预计阿那曲唑将于 2010 年 7 月和来曲唑将于 2011 年 6 月获得通用药物，在来曲唑获得通用药物之前，可能会存在财务压力，需要考虑让治疗初治的患者开始使用阿那曲唑而非来曲唑治疗，或让正在接受来曲唑治疗的患者转换为阿那曲唑治疗。
采用马尔可夫模型从美国医疗保健系统的角度评估了来曲唑与阿那曲唑治疗的成本效益。分别在治疗初治患者和正在接受来曲唑治疗的患者中评估了来曲唑与阿那曲唑的成本效益。对于后者，在根据内分泌治疗剩余年限定义的队列中，分别评估了继续使用来曲唑与将其转换为通用阿那曲唑（即治疗转换）的成本效益。假设将通用阿那曲唑用于治疗转换将导致另外 5%的患者停止接受内分泌治疗。BIG 1-98 号试验、ATAC 试验、早期乳腺癌试验者协作组关于他莫昔芬的荟萃分析以及其他已发表的资料报告了远处复发和死亡的概率。假设芳香化酶抑制剂的交叉效应与治疗持续时间成正比。假设芳香化酶抑制剂的成本在获得通用药物后将下降 75%。
在治疗初治患者中，使用来曲唑的总预期终生成本比使用阿那曲唑高 3916 美元。然而，开始使用来曲唑治疗可获得 0.15 个 QALY。与阿那曲唑相比，来曲唑的增量成本/QALY 为 25846 美元。对于正在接受来曲唑治疗的患者，与继续使用来曲唑相比，将其转换为阿那曲唑的治疗转换的总成本增加在所有队列中都在 4200 美元至 4500 美元之间。来曲唑治疗的 QALY 增益范围为 4 年内分泌治疗剩余年限的 0.21 个至 1 年治疗剩余年限的 0.13 个。增量成本/QALY 范围为 20276 美元至 34356 美元。
对于 HR+早期乳腺癌的绝经后女性，来曲唑治疗初治患者和正在接受来曲唑治疗的患者的成本效益可能优于阿那曲唑。本研究的局限性包括缺乏来曲唑和阿那曲唑的直接比较证据以及缺乏由于治疗转换而导致的芳香化酶抑制剂停药率的数据。
