Alternative trastuzumab dosing strategies in HER2-positive early breast cancer are associated with patient out-of-pocket savings.
Alternative trastuzumab dosing strategies in HER2-positive early breast cancer are associated with patient out-of-pocket savings.
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DOI：
10.1038/s41523-022-00393-2
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发表时间：
2022-03-14
影响因子：
5.9
通讯作者：
Ratain MJ
中科院分区：
文献类型：
--
作者：
Hsieh PH;Kacew AJ;Dreyer M;Serritella AV;Knoebel RW;Strohbehn GW;Ratain MJ
乳腺癌患者经常经历经济困难，通常是由于抗癌药物的高成本。我们试图开发替代曲妥珠单抗给药策略，比较其药代动力学有效性与标准给药，并评估过渡到它们的预期财务影响。我们从2017年至2019年期间在单一城市综合癌症中心接受曲妥珠单抗治疗的135例回顾性确定的HER 2阳性早期乳腺癌患者的记录中提取了临床数据。我们对一系列曲妥珠单抗剂量水平和频率进行了药代动力学模拟，通过曲妥珠单抗谷浓度（Ctrough）以及Ctrough超过曲妥珠单抗最低有效浓度（MEC）的人群和个体可能性评估疗效。我们进行了确定性财务建模，以估计替代给药策略的治疗相关财务节省。曲妥珠单抗维持剂量4 mg/kg每3周一次（Q3 W）和6 mg/kg每4周一次（Q4 W）的Ctrough高于MEC的概率与标准治疗6 mg/kg每3周一次几乎相同。在主要财务分析中，曲妥珠单抗4 mg/kg Q3 W和6 mg/kg Q4 W均与治疗期间显著的药物和给药相关自付费用节省相关，范围为765美元（新辅助治疗，Q4 W）至2791美元（辅助治疗，Q4 W）。特别是，Q4 W曲妥珠单抗增加了与工资损失和旅行费用避免相关的节省。在适当选择的患者中使用低剂量和降低频率的曲妥珠单抗可能会显著降低总药物利用率，并有意义地降低患者的经济毒性。前瞻性临床试验评估低剂量或降低频率的治疗性单克隆抗体的管理是必要的和必要的。
Patients with breast cancer frequently experience financial hardship, often due to the high costs of anti-cancer drugs. We sought to develop alternative trastuzumab dosing strategies, compare their pharmacokinetic effectiveness to standard dosing, and assess the expected financial implications of transitioning to them. We extracted clinical data from the records of 135 retrospectively identified patients with HER2-positive early breast cancer at a single, urban comprehensive cancer center who were treated with trastuzumab between 2017 and 2019. We performed pharmacokinetic simulations on a range of trastuzumab dose levels and frequencies, assessing efficacy by trough trastuzumab concentration (Ctrough) and population and individual likelihoods of Ctrough exceeding trastuzumab minimum effective concentration (MEC). We performed deterministic financial modeling to estimate the treatment-associated financial savings from alternative dosing strategies. Trastuzumab maintenance doses of 4 mg/kg every 3 weeks (Q3W) and 6 mg/kg every 4 weeks (Q4W) had nearly identical probabilities of Ctrough being above MEC as standard of care 6 mg/kg every 3 weeks. In the primary financial analysis, both trastuzumab 4 mg/kg Q3W and 6 mg/kg Q4W were associated with significant drug- and administration-related out-of-pocket cost savings over the duration of therapy, ranging from $765 (neoadjuvant, Q4W) to $2791 (adjuvant, Q4W). In particular, Q4W trastuzumab increased savings related to lost wages and travel cost avoidance. Low-dose and reduced frequency trastuzumab in appropriately selected patients may significantly reduce total drug utilization and meaningfully reduce patient financial toxicity. Prospective clinical trials evaluating low-dose or reduced-frequency administration of therapeutic monoclonal antibodies are warranted and needed.
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