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HER2 阳性乳腺癌的新辅助治疗策略:成本效益和生活质量结果。

Neoadjuvant treatment strategies for HER2-positive breast cancer: cost-effectiveness and quality of life outcomes.

机构信息

Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.

Yale School of Public Health, New Haven, CT, USA.

出版信息

Breast Cancer Res Treat. 2020 May;181(1):43-51. doi: 10.1007/s10549-020-05587-5. Epub 2020 Mar 17.

Abstract

PURPOSE

Achieving a pathologic complete response (pCR) with neoadjuvant therapy for HER2-positive breast cancer is associated with less recurrence and improved clinical outcomes compared to having residual cancer at surgery. However, recent data have demonstrated favorable outcomes for patients with residual HER2-positive cancer who received adjuvant trastuzumab emtansine (TDM-1). Therefore, we sought to determine the optimal chemotherapy/anti-HER2 treatment strategy.

METHODS

We created a decision-analytic model for patients with stage II-III HER2-positive cancer that incorporated utilities based on toxicity and recurrence. We separately modeled hormone receptor-negative (HR-) and positive (HR+) disease and calculated quality-adjusted life years (QALYs) and costs through 5 years. Simulated patients received one of the following neoadjuvant treatments: three 'intensive' regimens (TCHP: docetaxel, carboplatin, trastuzumab, pertuzumab; THP + AC: taxol, trastuzumab, pertuzumab then doxorubicin and cyclophosphamide; THP: taxol, trastuzumab, pertuzumab) and two 'de-escalated' regimens (TH: taxol, trastuzumab; TDM-1) followed by adjuvant treatment based on pathologic response.

RESULTS

Among 'intensive' neoadjuvant strategies, treatment with THP was more effective and less costly than TCHP or THP + AC. When 'de-escalated' strategies were included, TH became the most cost-effective. For HR-negative cancer, TH had 0.003 fewer quality-adjusted life years (QALYs) than THP but was less costly by $55,831, resulting in an incremental cost-effectiveness ratio of over $18M/QALY for THP, well above any threshold. For HR-positive cancer, neoadjuvant TH dominated the THP strategy.

CONCLUSION

An adaptive-treatment strategy beginning with neoadjuvant THP or TH followed by tailoring post-operative therapy reduces treatment costs, and spares toxicity compared to more intensive chemotherapy regimens for women with HER2-positive breast cancer.

摘要

目的

与手术时残留癌症相比,接受曲妥珠单抗恩坦辛(TDM-1)辅助治疗的残留 HER2 阳性癌症患者有较好的结局,因此新辅助治疗达到病理完全缓解(pCR)与复发减少和临床结局改善相关。然而,最近的数据显示残留 HER2 阳性癌症患者接受辅助曲妥珠单抗emtansine(TDM-1)治疗也有较好的结局。因此,我们旨在确定最佳的化疗/抗 HER2 治疗策略。

方法

我们为 HER2 阳性Ⅱ-Ⅲ期乳腺癌患者建立了一个决策分析模型,该模型纳入了基于毒性和复发的效用。我们分别对激素受体阴性(HR-)和阳性(HR+)疾病进行建模,并通过 5 年计算质量调整生命年(QALY)和成本。模拟患者接受以下新辅助治疗之一:三种“强化”方案(TCHP:多西他赛、卡铂、曲妥珠单抗、帕妥珠单抗;THP+AC:紫杉醇、曲妥珠单抗、帕妥珠单抗,然后阿霉素和环磷酰胺;THP:紫杉醇、曲妥珠单抗、帕妥珠单抗)和两种“简化”方案(TH:紫杉醇、曲妥珠单抗;TDM-1),然后根据病理反应进行辅助治疗。

结果

在“强化”新辅助策略中,与 TCHP 或 THP+AC 相比,THP 治疗更有效且成本更低。纳入“简化”策略后,TH 成为最具成本效益的方案。对于 HR-阴性癌症,TH 比 THP 少 0.003 个质量调整生命年(QALY),但成本低 55831 美元,THP 的增量成本效益比超过 1800 万美元/QALY,远高于任何阈值。对于 HR+癌症,新辅助 TH 优于 THP 策略。

结论

对于 HER2 阳性乳腺癌患者,从新辅助 THP 或 TH 开始的适应性治疗策略,然后根据术后治疗进行调整,可降低治疗成本,并减少毒性,优于更强化的化疗方案。

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