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J Natl Cancer Inst. 2012 Dec 5;104(23):1785-95. doi: 10.1093/jnci/djs433. Epub 2012 Nov 28.
In 2009, the American Society of Clinical Oncology recommended that patients with metastatic colorectal cancer (mCRC) who are candidates for anti-epidermal growth factor receptor (EGFR) therapy have their tumors tested for KRAS mutations because tumors with such mutations do not respond to anti-EGFR therapy. Limiting anti-EGFR therapy to those without KRAS mutations will reserve treatment for those likely to benefit while avoiding unnecessary costs and harm to those who would not. Similarly, tumors with BRAF genetic mutations may not respond to anti-EGFR therapy, though this is less clear. Economic analyses of mutation testing have not fully explored the roles of alternative therapies and resection of metastases.
This paper is based on a decision analytic framework that forms the basis of a cost-effectiveness analysis of screening for KRAS and BRAF mutations in mCRC in the context of treatment with cetuximab. A cohort of 50 000 patients with mCRC is simulated 10 000 times, with attributes randomly assigned on the basis of distributions from randomized controlled trials.
Screening for both KRAS and BRAF mutations compared with the base strategy (of no anti-EGFR therapy) increases expected overall survival by 0.034 years at a cost of $22 033, yielding an incremental cost-effectiveness ratio of approximately $650 000 per additional year of life. Compared with anti-EGFR therapy without screening, adding KRAS testing saves approximately $7500 per patient; adding BRAF testing saves another $1023, with little reduction in expected survival.
Screening for KRAS and BFAF mutation improves the cost-effectiveness of anti-EGFR therapy, but the incremental cost effectiveness ratio remains above the generally accepted threshold for acceptable cost effectiveness ratio of $100 000/quality adjusted life year.
2009 年,美国临床肿瘤学会建议转移性结直肠癌(mCRC)患者如果适合接受抗表皮生长因子受体(EGFR)治疗,应检测肿瘤的 KRAS 突变,因为此类突变的肿瘤对 EGFR 治疗无反应。将抗 EGFR 治疗限制在没有 KRAS 突变的患者中,可以保留对那些可能受益的患者的治疗,同时避免对那些不会受益的患者进行不必要的治疗和产生伤害。同样,具有 BRAF 基因突变的肿瘤可能对 EGFR 治疗无反应,但这一点不太明确。对突变检测的经济分析尚未充分探讨替代治疗和转移灶切除的作用。
本文基于决策分析框架,该框架构成了在曲妥珠单抗治疗背景下对 mCRC 中 KRAS 和 BRAF 突变筛查的成本效益分析的基础。模拟了 50000 例 mCRC 患者的队列,10000 次随机分配属性,这些属性基于随机对照试验的分布。
与基础策略(无抗 EGFR 治疗)相比,筛查 KRAS 和 BRAF 突变可使预期总生存期增加 0.034 年,成本为 22033 美元,增量成本效益比约为每额外增加 1 年生命 650000 美元。与未经筛选的抗 EGFR 治疗相比,添加 KRAS 检测可使每位患者节省约 7500 美元;添加 BRAF 检测可再节省 1023 美元,而预期生存时间略有下降。
KRAS 和 BFAF 突变筛查提高了抗 EGFR 治疗的成本效益,但增量成本效益比仍高于通常接受的 100000 美元/质量调整生命年的可接受成本效益比阈值。