Merck Serono Ltd, Bedfont Cross, Stanwell Road, Feltham, Middlesex, TW14 8NX, UK.
Mapi Group, Ltd, 73 Collier Street, London, N1 9BE, UK.
Appl Health Econ Health Policy. 2018 Aug;16(4):515-525. doi: 10.1007/s40258-018-0395-5.
Therapies may be more efficacious when targeting a patient subpopulation with specific attributes, thereby enhancing the cost-effectiveness of treatment. In the CRYSTAL study, patients with metastatic colorectal cancer (mCRC) were treated with cetuximab plus FOLFIRI or FOLFIRI alone until disease progression, unacceptable toxic effects or withdrawal of consent.
To determine if stratified use of cetuximab based on genetic biomarker detection improves cost-effectiveness.
We used individual patient data from CRYSTAL to compare the cost-effectiveness, cost per life-year (LY) and cost per quality-adjusted LY (QALY) gained of cetuximab plus FOLFIRI versus FOLFIRI alone in three cohorts of patients with mCRC: all randomised patients (intent-to-treat; ITT), tumours with no detectable mutations in codons 12 and 13 of exon 2 of the KRAS protein ('KRAS wt') and no detectable mutations in exons 2, 3 and 4 of KRAS and exons 2, 3 and 4 of NRAS ('RAS wt'). Survival analysis was conducted using RStudio, and a cost-utility model was modified to allow comparison of the three cohorts.
The deterministic base-case ICER (cost per QALY gained) was £130,929 in the ITT, £72,053 in the KRAS wt and £44,185 in the RAS wt cohorts for cetuximab plus FOLFIRI compared with FOLFIRI alone. At a £50,000 willingness-to-pay threshold, cetuximab plus FOLFIRI has a 2.8, 20 and 63% probability of being cost-effective for the ITT, KRAS wt and RAS wt cohorts, respectively, versus FOLFIRI alone.
Screening for mutations in both KRAS and NRAS may provide the most cost-effective approach to patient selection.
针对具有特定属性的患者亚群进行治疗可能更有效，从而提高治疗的成本效益。在 CRYSTAL 研究中，转移性结直肠癌（mCRC）患者接受西妥昔单抗联合 FOLFIRI 或 FOLFIRI 治疗，直至疾病进展、无法耐受的毒性反应或患者撤回同意。
确定基于遗传生物标志物检测的西妥昔单抗分层使用是否能提高成本效益。
我们使用 CRYSTAL 的个体患者数据，比较了西妥昔单抗联合 FOLFIRI 与 FOLFIRI 单独用于 mCRC 三种患者队列的成本效益、每生命年（LY）成本和每质量调整 LY（QALY）成本：所有随机患者（意向治疗；ITT）、KRAS 蛋白外显子 2 第 12 和 13 密码子无检测到突变（KRAS wt）且 KRAS 和 NRAS 外显子 2、3 和 4 无检测到突变的肿瘤（RAS wt）。使用 RStudio 进行生存分析，并修改成本效用模型以允许比较这三个队列。
在 ITT、KRAS wt 和 RAS wt 队列中，与 FOLFIRI 相比，西妥昔单抗联合 FOLFIRI 的每 QALY 增量成本（ICER）分别为每 QALY 增量成本 130929 英镑、72053 英镑和 44185 英镑。在 50000 英镑的意愿支付阈值下，与 FOLFIRI 相比，西妥昔单抗联合 FOLFIRI 对 ITT、KRAS wt 和 RAS wt 队列的成本效益分别为 2.8、20 和 63%。
筛查 KRAS 和 NRAS 突变可能是最具成本效益的患者选择方法。
