Aziz Mohamed Ismail Abdul, Tan Ling Eng, Tan Wan Hui Gloria, Toh Chee-Keong, Loke Lydia Pui Yee, Pearce Fiona, Ng Kwong
Agency for Care Effectiveness, Ministry of Health, Singapore, Singapore.
Division of Medical Oncology, National Cancer Centre, Singapore, Singapore.
J Med Econ. 2020 Sep;23(9):952-960. doi: 10.1080/13696998.2020.1775620. Epub 2020 Jun 22.
To assess the cost-effectiveness of pembrolizumab monotherapy compared with standard chemotherapy for the treatment of advanced non-small cell lung cancer (NSCLC) in previously untreated adults who have a high programmed death ligand 1 (PD-L1) tumor proportion score of 50% or greater in Singapore. A partitioned-survival analysis model was developed from a healthcare system's perspective that extrapolated clinical and economic outcomes of first-line pembrolizumab (maximum treatment duration of 2 years) versus platinum doublet chemotherapy over a 10-year time horizon for patients with advanced NSCLC. The model consisted of three health states: alive with no progression, alive with progression, and dead. Key clinical inputs were based on Kaplan-Meier survival curves from the interim (median follow-up = 11.2 months) and updated analysis (median follow-up = 25.2 months) of the KEYNOTE-024 randomized controlled trial. Local cost data were applied. Utilities were derived from published international estimates. Both one-way and multivariate probabilistic sensitivity analyses (PSA) were conducted to identify key drivers of the results. Using the results from the updated analysis of KEYNOTE-024, patients treated with pembrolizumab experienced more quality adjusted life-years (QALYs), but incurred higher costs compared to chemotherapy over a 10-year time horizon (pembrolizumab: 1.9983 QALYs, SGD215,761; chemotherapy: 1.1317 QALYs, SGD70,444). The base-case incremental cost-effectiveness ratio (ICER) was SGD167,692 per QALY gained. One-way sensitivity analysis showed the ICER was most sensitive to the cost of pembrolizumab, followed by the time horizon. Multivariate PSA indicated that pembrolizumab had 0% probability of being cost-effective at a hypothetical willingness-to-pay threshold of SGD100,000 per QALY gained. While pembrolizumab is superior to standard chemotherapy in improving overall survival and progression-free survival, results suggest that it is unlikely to be cost-effective at its current price in Singapore. Factors including clinical effectiveness, safety, and budget impact should also be considered when making national funding decisions.
为评估帕博利珠单抗单药治疗与标准化疗相比,用于治疗新加坡既往未接受过治疗、程序性死亡配体1(PD-L1)肿瘤比例评分达到50%或更高的晚期非小细胞肺癌(NSCLC)成人患者的成本效益。从医疗保健系统的角度开发了一种分区生存分析模型,该模型推断了一线帕博利珠单抗(最长治疗持续时间为2年)与铂类双联化疗在10年时间范围内对晚期NSCLC患者的临床和经济结局。该模型包括三种健康状态:无进展存活、进展存活和死亡。关键临床输入基于KEYNOTE-024随机对照试验中期(中位随访时间 = 11.2个月)和更新分析(中位随访时间 = 25.2个月)的Kaplan-Meier生存曲线。应用了当地成本数据。效用值来自已发表的国际估计值。进行了单因素和多因素概率敏感性分析(PSA)以确定结果的关键驱动因素。使用KEYNOTE-024更新分析的结果,在10年时间范围内,接受帕博利珠单抗治疗的患者获得了更多的质量调整生命年(QALY),但与化疗相比成本更高(帕博利珠单抗:1.9983 QALY,215,761新元;化疗:1.1317 QALY,70,444新元)。基础病例增量成本效益比(ICER)为每获得一个QALY 167,692新元。单因素敏感性分析表明,ICER对帕博利珠单抗的成本最敏感,其次是时间范围。多因素PSA表明,在假设每获得一个QALY支付意愿阈值为100,000新元的情况下,帕博利珠单抗具有成本效益的概率为0%。虽然帕博利珠单抗在改善总生存期和无进展生存期方面优于标准化疗,但结果表明,以其目前在新加坡的价格,不太可能具有成本效益。在做出国家资助决策时,还应考虑包括临床疗效、安全性和预算影响等因素。