■NCT01970865试验的ALTA-1L试验和EXP-3B组发现,布格替尼和氯拉替尼在治疗ALK阳性非小细胞肺癌(NSCLC)患者中都表现出持久和稳健的反应。然而,Brigatinib和lorlatinib治疗费用高,需要无限期给药直至疾病进展.因此,与在化疗后保留这两种药物直至进展相比,在化疗前使用布加替尼和氯拉替尼是否具有成本效益仍不确定.
■我们使用马尔可夫模型来评估ALK阳性NSCLC患者在化疗前用布加替尼治疗的临床结果和医疗保健成本,以及在化疗后保留这些药物直至进展的策略。使用基于多个临床试验的参数生存建模来估计转移概率。药品采购成本,不良事件成本,管理成本从之前发表的研究和公开数据中提取.我们计算了终身直接医疗成本,质量调整寿命年(QALYs),从美国付款人的角度来看,以及增量成本效益比。
■我们的基本案例分析表明,与二线布格替尼和洛拉替尼相比,使用一线布格替尼和洛拉替尼的成本效益比增加$-400,722.09/QALY,这意味着二线布格替尼和洛拉替尼的成本更低,结局更好。单因素敏感性分析显示结果对布加替尼的成本最为敏感。概率敏感性分析显示,在化疗前使用布格替尼和洛拉替尼的成本效益概率为0%,而在化疗后将这两种药物延迟至进展,每个QALY的支付意愿阈值为150,000美元。进行的灵敏度分析揭示了这一结果的稳健性,因为增量成本效益比从未超过支付意愿阈值。
■从美国付款人的角度来看,考虑到目前的定价,使用布格替尼作为一线治疗,然后使用氯拉替尼治疗ALK阳性非小细胞肺癌可能不划算。延迟布加替尼,然后再进行氯拉替尼,直到随后的治疗线可能是一个合理的策略,可以限制医疗保健成本而不影响临床结果。在这种情况下,需要更成熟的数据来更好地估计成本效益。
The ALTA-1 L trial and EXP-3B arm of NCT01970865 trial found that both
brigatinib and lorlatinib showed durable and robust responses in treating ALK-positive non-small cell lung cancer (NSCLC) patients. However,
brigatinib and lorlatinib treatments are costly and need indefinite administration until the disease progression. Thus, it remains uncertain whether using brigatinib followed by lorlatinib before chemotherapy is cost-effective compared to reserving these two drugs until progression after chemotherapy.
We used a Markov model to assess clinical outcomes and healthcare costs of treating ALK-positive NSCLC individuals with brigatinib followed by lorlatinib before chemotherapy versus a strategy of reserving these drugs until progression after chemotherapy. Transition probabilities were estimated using parametric survival modeling based on multiple clinical trials. The drug acquisition costs, adverse events costs, administration costs were extracted from published studies before and publicly available data. We calculated lifetime direct healthcare costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios from the perspective of a United States payer.
Our base-case analysis indicated that the incremental cost-effectiveness ratios of using first-line brigatinib followed by lorlatinib compared with second-line brigatinib followed by lorlatinib is $-400,722.09/QALY which meant that second-line
brigatinib followed by lorlatinib had less costs and better outcomes. Univariate sensitivity analysis indicated the results were most sensitive to the cost of
brigatinib. Probability sensitivity analysis revealed that using brigatinib followed by lorlatinib before chemotherapy had a 0% probability of cost-effectiveness versus delaying these two drugs until progression after chemotherapy at a willingness-to-pay threshold of $150,000 per QALY. Sensitivity analyses conducted revealed the robustness of this result, as incremental cost-effectiveness ratios never exceeded the willingness-to-pay threshold.
Using
brigatinib as first-line treatment followed by lorlatinib for ALK-positive NSCLC may not be cost-effective given current pricing from the perspective of a United States payer. Delaying brigatinib followed by lorlatinib until subsequent lines of treatment may be a reasonable strategy that could limit healthcare costs without affecting clinical outcomes. More mature data are needed to better estimate cost-effectiveness in this setting.