Kwong Ava, Leung Roland, Chan Tsz Ching, Khandelwal Anvi, Mishra Kshama, Huang Min
Department of Surgery, The University of Hong Kong, Pok Fu Lam, Hong Kong SAR, China.
Division of Hematology and Medical Oncology, Department of Medicine, Queen Mary Hospital, Pok Fu Lam, Hong Kong SAR, China.
Oncol Ther. 2024 Sep;12(3):525-547. doi: 10.1007/s40487-024-00285-4. Epub 2024 Jul 22.
The phase III randomized KEYNOTE-522 trial demonstrated that pembrolizumab in combination with chemotherapy as neoadjuvant treatment followed by adjuvant pembrolizumab (pembrolizumab + chemotherapy) provided significant improvements in event-free survival (EFS) and overall survival (OS) for patients with high-risk early-stage triple-negative breast cancer (eTNBC). The objective was to assess the cost-effectiveness of pembrolizumab + chemotherapy compared to neoadjuvant chemotherapy alone (chemotherapy) in patients with high-risk eTNBC from a Hong Kong third-party payer perspective.
A multistate transition model with four health states (event-free), locoregional recurrence, distant metastases, and death) was developed to assess the lifetime medical costs and health outcomes (3% annual discount), along with incremental cost-effectiveness ratios (ICERs) using efficacy and safety data from the KEYNOTE-522 trial. The health state utilities were derived from KEYNOTE-522 Euro-QoL-five-dimension five-level questionnaire (EQ-5D-5L) data. Costs were expressed in 2022 Hong Kong dollars (HKD). Scenario and sensitivity analyses were performed to assess the robustness of results.
Over a 32-year time horizon, base case results showed that pembrolizumab + chemotherapy was associated with a 3.42 year longer EFS and expected gains of 3.05 life years (LYs) and 2.45 quality-adjusted life years (QALYs) compared to chemotherapy. The resultant ICERs were HKD 135,200 per QALY gained and HKD 108,463 per LY gained, which were lower than the World Health Organization (WHO) cost-effectiveness threshold of three times gross domestic product (GDP) per capita for Hong Kong of HKD 1,171,308 per QALY. The one-way sensitivity analyses (OWSA) and probabilistic sensitivity analysis (PSA) showed the results were robust across various inputs and alternative scenarios.
On the basis of the analysis conducted for a 56-year-old cohort with high-risk eTNBC and assumptions in the model, pembrolizumab + chemotherapy represents a cost-effective proposition (as the ICER is approximately 35% of the GDP per capita in Hong Kong) for patients with high-risk eTNBC in Hong Kong.
III期随机KEYNOTE-522试验表明，帕博利珠单抗联合化疗作为新辅助治疗，随后进行辅助帕博利珠单抗治疗（帕博利珠单抗+化疗），可使高危早期三阴性乳腺癌（eTNBC）患者的无事件生存期（EFS）和总生存期（OS）得到显著改善。目的是从香港第三方支付方的角度评估帕博利珠单抗+化疗与单纯新辅助化疗（化疗）相比，在高危eTNBC患者中的成本效益。
建立了一个具有四个健康状态（无事件、局部区域复发、远处转移和死亡）的多状态转换模型，以评估终身医疗成本和健康结局（3%的年度贴现率），并使用KEYNOTE-522试验的疗效和安全性数据计算增量成本效益比（ICER）。健康状态效用值来自KEYNOTE-522欧洲五维五级问卷（EQ-5D-5L）数据。成本以2022年港元（HKD）表示。进行了情景分析和敏感性分析，以评估结果的稳健性。
在32年的时间范围内，基础病例结果显示，与化疗相比，帕博利珠单抗+化疗的EFS延长了3.42年，预期寿命增加3.05年（LYs），质量调整生命年（QALYs）增加2.45年。由此产生的ICER为每获得一个QALY 135,200港元，每获得一个LY 108,463港元，低于世界卫生组织（WHO）设定的成本效益阈值，即香港人均国内生产总值（GDP）的三倍，为每QALY 1,171,308港元。单因素敏感性分析（OWSA）和概率敏感性分析（PSA）表明，在各种输入和替代情景下，结果都是稳健的。
基于对56岁高危eTNBC队列的分析以及模型中的假设，帕博利珠单抗+化疗对于香港高危eTNBC患者来说是一个具有成本效益的方案（因为ICER约为香港人均GDP的35%）。
