Attard C L, Pepper A N, Brown S T, Thompson M F, Thuresson P-O, Yunger S, Dent S, Paterson A H, Wells G A
Cornerstone Research Group Inc. , Burlington, ON , Canada.
J Med Econ. 2015 Mar;18(3):173-88. doi: 10.3111/13696998.2014.979938. Epub 2014 Nov 10.
The NeoSphere trial demonstrated that the addition of pertuzumab to trastuzumab and docetaxel for the neoadjuvant treatment of HER2-positive locally advanced, inflammatory, or early breast cancer (eBC) resulted in a significant improvement in pathological complete response (pCR). Furthermore, the TRYPHAENA trial supported the benefit of neoadjuvant dual anti-HER2 therapy. Survival data from these trials is not yet available; however, other studies have demonstrated a correlation between pCR and improved event-free survival (EFS) and overall survival (OS) in this patient population. This study represents the first Canadian cost-effectiveness analysis of pertuzumab in the neoadjuvant treatment of HER2-positive eBC.
A cost-utility analysis (CUA) was conducted using a three health state Markov model ('event-free', 'relapsed', and 'dead'). Two separate analyses were conducted; the first considering total pCR (ypT0/is ypN0) data from NeoSphere, and the second from TRYPHAENA. Published EFS and OS data partitioned for patients achieving/not achieving pCR were used in combination with the percentage achieving pCR in the pertuzumab trials to estimate survival. This CUA included published utility values and direct medical costs including drugs, treatment administration, management of adverse events, supportive care, and subsequent therapy. To address uncertainty, a probabilistic sensitivity analysis (PSA) and alternative scenarios were explored.
Both analyses suggested that the addition of pertuzumab resulted in increased life-years and quality-adjusted life-years (QALYs). The incremental cost per QALY ranged from $25,388 (CAD; NeoSphere analysis) to $46,196 (TRYPHAENA analysis). Sensitivity analyses further support the use of pertuzumab, with cost-effectiveness ratios ranging from $9230-$64,421. At a threshold of $100,000, the addition of pertuzumab was cost-effective in nearly all scenarios (93% NeoSphere; 79% TRYPHAENA).
Given the improvement in clinical efficacy and a favorable cost per QALY, the addition of pertuzumab in the neoadjuvant setting represents an attractive treatment option for HER2-positive eBC patients.
NeoSphere试验表明，在曲妥珠单抗和多西他赛基础上加用帕妥珠单抗用于HER2阳性局部晚期、炎性或早期乳腺癌（eBC）的新辅助治疗，可显著提高病理完全缓解（pCR）率。此外，TRYPHAENA试验支持新辅助双抗HER2治疗的益处。这些试验的生存数据尚未可得；然而，其他研究已证明在该患者群体中pCR与无事件生存期（EFS）和总生存期（OS）改善之间存在相关性。本研究是加拿大首次对帕妥珠单抗用于HER2阳性eBC新辅助治疗进行的成本效益分析。
采用三健康状态马尔可夫模型（“无事件”、“复发”和“死亡”）进行成本效用分析（CUA）。进行了两项独立分析；第一项分析考虑了来自NeoSphere的总pCR（ypT0/is ypN0）数据，第二项分析来自TRYPHAENA。已发表的按达到/未达到pCR划分的EFS和OS数据与帕妥珠单抗试验中达到pCR的百分比相结合，用于估计生存期。该CUA纳入了已发表的效用值和直接医疗成本，包括药物、治疗给药、不良事件管理、支持性护理及后续治疗。为解决不确定性问题，进行了概率敏感性分析（PSA）并探讨了替代方案。
两项分析均表明，加用帕妥珠单抗可增加生命年和质量调整生命年（QALY）。每QALY的增量成本范围为25,388加元（NeoSphere分析）至46,196加元（TRYPHAENA分析）。敏感性分析进一步支持使用帕妥珠单抗，成本效益比范围为9230 - 64,421加元。在100,000加元的阈值下，加用帕妥珠单抗在几乎所有情况下均具有成本效益（NeoSphere为93%；TRYPHAENA为79%）。
鉴于临床疗效的改善以及每QALY成本效益良好，在新辅助治疗中加用帕妥珠单抗对HER2阳性eBC患者而言是一种有吸引力的治疗选择。
