Millar J Alasdair, Millward Michael J
Department of Internal Medicine, Royal Perth Hospital, Perth, Western Australia, Australia.
Pharmacoeconomics. 2007;25(5):429-42. doi: 10.2165/00019053-200725050-00006.
Recent randomised trials have demonstrated a statistically significant effect of trastuzumab on disease-free survival when used as adjuvant therapy for human epidermal growth factor receptor 2 protein (HER2)-positive resectable early stage breast cancer, with a treatment course lasting either 9 or 52 weeks. However, the cost effectiveness of adjuvant trastuzumab with respect to mortality remains uncertain, especially in an Australian setting.
To estimate the cost effectiveness of trastuzumab in Australia, in a cohort of 50-year-old patients with HER2-positive breast cancer over a lifetime, using (i) disease-free survival and cardiotoxicity data from recent randomised trials; (ii) information on long-term survival of patients with treated primary breast cancer; and (iii) costs of treating local and distant relapses and disease from causes other than breast cancer.
A Markov model consisting of four health states (remission, loco-regional recurrence, metastatic disease and death) was developed. Transition probabilities corresponded to patterns of relapse and metastases seen in recent trials. The model was run until age 100 years to allow calculation of average survival. Outcome measures were life-years and QALYs (calculated using utility weights reported in the literature). The model was calibrated to reflect literature evidence that the risk of breast cancer recurrence following primary treatment diminishes progressively to zero after about 20 years. It was assumed that the morbidity benefit of trastuzumab observed in trials would be present for 5 years but would then diminish progressively to zero after 8 years. Costs (year 2005 values) and benefits were discounted at 3% per annum.
For every 1000 patients treated with a 52-week course of trastuzumab, there were 136 fewer breast cancer deaths (relative risk reduction 28%). The incremental cost-effectiveness ratios (ICERs) were Australian dollars ($ A)13 730 per year of life saved (YOLS) and $ A22 793 per QALY. The net incremental cost was $ A56.3 million ($ A414 012/cancer death avoided). Cost effectiveness declined (ICER = $ A27 734/QALY) in older patients (age 65 years at treatment initiation). The ICER was driven mainly by the drug acquisition costs, the assumption of the duration of benefit and the discount rate. Cost offsets from reduced costs of treating recurrent or metastatic breast cancer during follow-up were present but these factors were of less importance according to sensitivity analyses. The 9-week treatment schedule approached economic dominance (ICER = $ A1700/QALY) because of decreased costs, improved relative risk for prevention of metastases and more cancer deaths avoided (196).
The results suggest that trastuzumab as adjuvant therapy for early breast cancer may be cost effective when given over either 52 or 9 weeks at current acquisition costs in Australia. However, the overall budget impact of the 52-week course is significant, and the 9-week course appears economically attractive.
近期的随机试验表明，曲妥珠单抗作为人表皮生长因子受体2蛋白（HER2）阳性可切除早期乳腺癌的辅助治疗药物，治疗疗程为9周或52周时，对无病生存期具有统计学上的显著影响。然而，辅助使用曲妥珠单抗对死亡率的成本效益仍不确定，尤其是在澳大利亚的情况下。
利用（i）近期随机试验中的无病生存期和心脏毒性数据；（ii）原发性乳腺癌治疗患者的长期生存信息；（iii）治疗局部和远处复发以及非乳腺癌所致疾病的成本，估计在澳大利亚，一组50岁HER2阳性乳腺癌患者一生中使用曲妥珠单抗的成本效益。
建立了一个由四个健康状态（缓解、局部区域复发、转移性疾病和死亡）组成的马尔可夫模型。转移概率与近期试验中观察到的复发和转移模式相对应。该模型运行至100岁，以计算平均生存期。结果指标为生命年和质量调整生命年（使用文献中报告的效用权重计算）。该模型经过校准，以反映文献证据，即初次治疗后乳腺癌复发风险在约20年后逐渐降至零。假设试验中观察到的曲妥珠单抗的发病益处将持续5年，但在8年后将逐渐降至零。成本（2005年值）和效益按每年3%进行贴现。
每1000例接受52周曲妥珠单抗治疗的患者中，乳腺癌死亡人数减少136例（相对风险降低28%）。增量成本效益比（ICER）为每挽救一年生命（YOLS）13730澳元，每质量调整生命年22793澳元。净增量成本为5630万澳元（每避免一例癌症死亡414012澳元）。在老年患者（开始治疗时年龄为65岁）中，成本效益有所下降（ICER =每质量调整生命年27734澳元）。ICER主要由药物购置成本、效益持续时间假设和贴现率驱动。随访期间复发性或转移性乳腺癌治疗成本降低带来了成本抵消，但根据敏感性分析，这些因素的重要性较低。9周治疗方案接近经济学优势（ICER =每质量调整生命年1700澳元），因为成本降低、预防转移的相对风险改善以及避免的癌症死亡人数更多（196例）。
结果表明，在澳大利亚当前的购置成本下，曲妥珠单抗作为早期乳腺癌的辅助治疗药物，无论是给药52周还是9周，可能都具有成本效益。然而，52周疗程对总体预算的影响很大，而9周疗程在经济上似乎更具吸引力。
