Lauren Brianna, Ostvar Sassan, Silver Elisabeth, Ingram Myles, Oh Aaron, Kumble Lindsay, Laszkowska Monika, Chu Jacqueline N, Hershman Dawn L, Manji Gulam, Neugut Alfred I, Hur Chin
Columbia University Medical Center, New York, NY, USA.
Massachusetts General Hospital, Boston, MA, USA.
J Oncol. 2020 Feb 17;2020:2198960. doi: 10.1155/2020/2198960. eCollection 2020.
The 5-year survival rate of patients with metastatic gastric cancer (GC) is only 5%. However, trials have demonstrated promising antitumor activity for targeted therapies/immunotherapies among chemorefractory metastatic GC patients. Pembrolizumab has shown particular efficacy among patients with programmed death ligand-1 (PD-L1) expression and high microsatellite instability (MSI-H). The aim of this study was to assess the effectiveness and cost-effectiveness of biomarker-guided second-line GC treatment.
We constructed a Markov decision-analytic model using clinical trial data. Our model compared pembrolizumab monotherapy and ramucirumab/paclitaxel combination therapy for all patients and pembrolizumab for patients based on MSI status or PD-L1 expression. Paclitaxel monotherapy and best supportive care for all patients were additional comparators. Costs of drugs, treatment administration, follow-up, and management of adverse events were estimated from a US payer perspective. The primary outcomes were quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) with a willingness-to-pay threshold of $100,000/QALY over 60 months. Secondary outcomes were unadjusted life years (survival) and costs. Deterministic and probabilistic sensitivity analyses were performed to evaluate model uncertainty.
The most effective strategy was pembrolizumab for MSI-H patients and ramucirumab/paclitaxel for all other patients, adding 3.8 months or 2.0 quality-adjusted months compared to paclitaxel. However, this strategy resulted in a prohibitively high ICER of $1,074,620/QALY. The only cost-effective strategy was paclitaxel monotherapy for all patients, with an ICER of $53,705/QALY.
Biomarker-based treatments with targeted therapies/immunotherapies for second-line metastatic GC patients substantially improve unadjusted and quality-adjusted survival but are not cost-effective at current drug prices.
转移性胃癌（GC）患者的5年生存率仅为5%。然而，试验已证明靶向治疗/免疫治疗在化疗难治性转移性GC患者中具有可观的抗肿瘤活性。帕博利珠单抗在程序性死亡配体-1（PD-L1）表达和高微卫星不稳定性（MSI-H）的患者中显示出特别的疗效。本研究的目的是评估生物标志物指导的二线GC治疗的有效性和成本效益。
我们使用临床试验数据构建了一个马尔可夫决策分析模型。我们的模型比较了帕博利珠单抗单药治疗与雷莫西尤单抗/紫杉醇联合治疗对所有患者的效果，以及根据MSI状态或PD-L1表达对患者使用帕博利珠单抗的效果。紫杉醇单药治疗和对所有患者的最佳支持治疗是额外的比较对象。从美国支付方的角度估算了药物、治疗给药、随访和不良事件管理的成本。主要结局是质量调整生命年（QALYs）和增量成本效益比（ICERs），支付意愿阈值为60个月内100,000美元/QALY。次要结局是未调整生命年（生存率）和成本。进行了确定性和概率敏感性分析以评估模型的不确定性。
最有效的策略是对MSI-H患者使用帕博利珠单抗，对所有其他患者使用雷莫西尤单抗/紫杉醇，与紫杉醇相比增加了3.8个月或2.0个质量调整月。然而，该策略导致ICER高得令人望而却步，为1,074,620美元/QALY。唯一具有成本效益的策略是对所有患者使用紫杉醇单药治疗，ICER为53,705美元/QALY。
针对二线转移性GC患者的基于生物标志物的靶向治疗/免疫治疗可显著改善未调整和质量调整后的生存率，但按当前药物价格并不具有成本效益。
