Personalised Oncology Division, Walter and Eliza Hall Institute, 1G Royal Parade, Parkville, Melbourne, VIC, 3052, Australia.
Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
Pharmacoeconomics. 2021 Aug;39(8):953-964. doi: 10.1007/s40273-021-01047-0. Epub 2021 Jun 5.
Substantial adjuvant chemotherapy (AC) overtreatment for stage II colorectal cancer results in a health and financial burden. Circulating tumour DNA (ctDNA) can improve patient selection for AC by detecting micro-metastatic disease. We estimated the health economic potential of ctDNA-guided AC for stage II colorectal cancer.
A cost-utility analysis was performed to compare ctDNA-guided AC to standard of care, where 22.6% of standard of care patients and all ctDNA-positive patients (8.7% of tested patients) received AC and all ctDNA-negative patients (91.3%) did not. A third preference-sensitive ctDNA strategy was included where 6.8% of ctDNA-negative patients would receive AC. A state-transition model was populated using data from a prospective cohort study and clinical registries. Health and economic outcomes were discounted at 5% over a lifetime horizon from a 2019 Australian payer perspective. Extensive scenario and probabilistic analyses quantified model uncertainty.
Compared to standard of care, the ctDNA and preference-sensitive ctDNA strategies increased quality-adjusted life-years by 0.20 (95% confidence interval - 0.40 to 0.81) and 0.19 (- 0.40 to 0.78), and resulted in incremental costs of AUD - 4055 (- 16,853 to 8472) and AUD - 2284 (- 14,685 to 10,116), respectively. Circulating tumour DNA remained cost effective at a willingness to pay of AUD 20,000 per quality-adjusted life-year gained throughout most scenario analyses in which the proportion of ctDNA-positive patients cured by AC and compliance to a ctDNA-negative test results were decreased.
Circulating tumour-guided AC is a potentially cost-effective strategy towards reducing overtreatment in stage II colorectal cancer. Results from ongoing randomised clinical studies will be important to reduce uncertainty in the estimates.
对 II 期结直肠癌进行大量辅助化疗（AC）过度治疗会导致健康和经济负担。循环肿瘤 DNA（ctDNA）通过检测微转移疾病，可以提高 AC 患者的选择。我们评估了 ctDNA 指导 II 期结直肠癌 AC 的健康经济学潜力。
进行了一项成本效用分析，以比较 ctDNA 指导的 AC 与标准治疗。标准治疗组中 22.6%的患者和所有 ctDNA 阳性患者（测试患者的 8.7%）接受了 AC，而所有 ctDNA 阴性患者（91.3%）未接受 AC。还纳入了一种对 ctDNA 有第三偏好的策略，其中 6.8%的 ctDNA 阴性患者将接受 AC。使用前瞻性队列研究和临床登记处的数据填充状态转换模型。从 2019 年澳大利亚支付者的角度来看，健康和经济结果在终生范围内以 5%的贴现率进行贴现。广泛的情景和概率分析量化了模型不确定性。
与标准治疗相比，ctDNA 和对 ctDNA 有第三偏好的策略分别增加了 0.20（95%置信区间-0.40 至 0.81）和 0.19（-0.40 至 0.78）的质量调整生命年，增量成本分别为-4055 澳元（-16853 至 8472 澳元）和-2284 澳元（-14685 至 10116 澳元）。在大多数情况下，ctDNA 仍然具有成本效益，在支付意愿为 20000 澳元/质量调整生命年时，AC 治愈的 ctDNA 阳性患者比例和对 ctDNA 阴性检测结果的依从性降低。
循环肿瘤指导的 AC 是减少 II 期结直肠癌过度治疗的潜在成本效益策略。正在进行的随机临床试验的结果将对降低估计的不确定性非常重要。
