Krebs Emanuel, Weymann Deirdre, Ho Cheryl, Weppler Alison, Bosdet Ian, Karsan Aly, Hanna Timothy P, Pollard Samantha, Regier Dean A
Cancer Control Research, BC Cancer Research Institute, Vancouver, BC, Canada.
Faculty of Health Sciences, Simon Fraser University, Vancouver, BC.
JCO Precis Oncol. 2025 Jan;9:e2400631. doi: 10.1200/PO-24-00631. Epub 2025 Feb 21.
Targeted therapy and immunotherapy promise improved survival in patients with advanced melanoma, yet the effectiveness and cost-effectiveness of multigene panel sequencing compared with single-gene testing to guide therapeutic decisions is unknown.
Our population-based quasi-experimental retrospective target trial emulation used comprehensive patient-level data for 364 British Columbia, Canada, adults with an advanced melanoma diagnosis receiving multigene panel sequencing or single-gene testing between September 1, 2016, and December 31, 2018. We 1:1 matched multigene panel patients to controls using genetic algorithm-based matching. Outcomes included 3-year overall survival (OS) and health care costs (2021 Canadian dollars [CAD]) with incremental net monetary benefit for life-years gained (LYG). Outcomes were analyzed using inverse probability of censoring weighted linear regression for the intention-to-treat (ITT) effect. The per-protocol (PP) effect estimation also included stabilized inverse probability of treatment weights. We then used Weibull regression and Kaplan-Meier survival analysis.
We matched 147 multigene panel patients to controls, achieving balance for all covariates. After matching, ITT incremental costs were $19,447 CAD (95% CI, -$18,516 to $76,006) and incremental LYG were 0.22 (95% CI, -0.05 to 0.49). We found uncertainty in differences on OS using Kaplan-Meier ( = .11) and Weibull regression (hazard ratio [HR], 0.73 [95% CI, 0.51 to 1.03]) in the ITT. PP incremental costs were $36,367 CAD (95% CI, -$6,653 to $120,216]) and incremental LYG were 0.56 (95% CI, 0.39 to 1.24), with corresponding differences in OS using Kaplan-Meier ( = .02) and Weibull regression (HR, 0.56 [95% CI, 0.36 to 0.87]). The probability of multigene panels being cost-effective at $100,000/LYG CAD was 55% for ITT and 65% for PP.
The cost-effectiveness of multigene panels was evenly poised at higher thresholds, even when accounting for treatment initiation. Health systems reimbursing multigene panels and expensive therapies may be confronted with a value tradeoff, in which there may be improved survival albeit with a modest change in cost-effectiveness.
靶向治疗和免疫治疗有望提高晚期黑色素瘤患者的生存率，但与单基因检测相比，多基因检测指导治疗决策的有效性和成本效益尚不清楚。
我们基于人群的准实验性回顾性目标试验模拟使用了加拿大不列颠哥伦比亚省364名成年晚期黑色素瘤患者的综合患者层面数据，这些患者在2016年9月1日至2018年12月31日期间接受了多基因检测或单基因检测。我们使用基于遗传算法的匹配方法将多基因检测患者与对照组进行1:1匹配。结果包括3年总生存率（OS）和医疗保健成本（2021加元[CAD]），以及生命年增益（LYG）的增量净货币效益。使用逆概率删失加权线性回归分析意向性治疗（ITT）效应的结果。按方案（PP）效应估计还包括稳定的治疗权重逆概率。然后我们使用威布尔回归和卡普兰-迈耶生存分析。
我们将147名多基因检测患者与对照组进行了匹配，所有协变量均达到平衡。匹配后，ITT增量成本为19,447加元（95%CI，-18,516至76,006加元），增量LYG为0.22（95%CI，-0.05至0.49）。我们发现，在ITT中，使用卡普兰-迈耶（P = 0.11）和威布尔回归（风险比[HR]，0.73[95%CI，0.51至1.03]）分析OS差异时存在不确定性。PP增量成本为36,367加元（95%CI，-6,653至120,216加元），增量LYG为0.56（95%CI，0.39至1.24），使用卡普兰-迈耶（P = 0.02）和威布尔回归（HR，0.56[9
