Health Economics and Outcomes Research, Pfizer Inc., San Francisco, CA, USA.
Statistics, Pfizer Inc., New York, NY, USA.
Adv Ther. 2019 Mar;36(3):708-720. doi: 10.1007/s12325-018-0867-x. Epub 2019 Jan 17.
INTRODUCTION: With evolving treatment guidelines for germline BRCA1/2 mutation (gBRCAm) in breast cancer, we present the latest gBRCA testing rates among metastatic breast cancer (mBC) patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) or triple-negative breast cancer (TNBC). Among these patients with gBRCAm, we analyzed clinical outcomes, treatment patterns, and health resource utilization (HRU). METHODS: The Flatiron Health electronic health record database was used to assess gBRCA testing rates in a real-world retrospective analysis of US patients at least 18 years old with HR+/HER2- or TNBC, and with mBC diagnosed from January 2011 to February 2018. Outcomes were compared between gBRCAm patients with HR+/HER2- vs TNBC, adjusting for imbalances utilizing inverse probability treatment weighting; effects of HR+/HER2- vs TNBC on overall survival (OS) were assessed, antineoplastic treatments summarized, and HRU analyzed using t tests. RESULTS: The study included 12,021 mBC patients (HR+/HER2-, 10,291; TNBC, 1730). Results for gBRCA testing were available for 2005 (16.7%) patients (HR+/HER2-, 1587; TNBC, 418). A total of 229 (1.9%) patients (HR+/HER2-, 165; TNBC, 64) had gBRCAm. Significantly worse OS in gBRCAm mBC was observed in TNBC vs HR+/HER2- [hazard ratio (95% confidence interval), 0.45 (0.27-0.74); p = 0.002]. Estimated median and 4-year OS rates for gBRCAm mBC patients with either HR+/HER2- or TNBC were 38.0 months, 23.4 months and 35.6%, 21.2% respectively. The most common first-line treatment post diagnosis for gBRCAm HR+/HER2- was letrozole (8%) vs capecitabine (14%) for gBRCAm TNBC. The number of HRU treatment visits per patient per year was significantly (p < 0.05) higher among gBRCAm mBC patients with TNBC vs HR+/HER2-. CONCLUSION: Among HER2- mBC patients, gBRCA testing rates are low. Among gBRCAm HER2- mBC patients, the poor OS and HRU burden observed, especially in patients with TNBC, demonstrate an unmet need for more efficacious, targeted, and less HRU-intensive treatment options. FUNDING: Pfizer.
介绍：随着胚系 BRCA1/2 突变（gBRCAm）治疗指南的不断发展，我们报告了激素受体阳性/人表皮生长因子受体 2 阴性（HR+/HER2-）或三阴性乳腺癌（TNBC）转移性乳腺癌（mBC）患者中最新的 gBRCA 检测率。在这些 gBRCAm 患者中，我们分析了临床结局、治疗模式和健康资源利用（HRU）。
方法：利用 Flatiron Health 电子病历数据库，对 2011 年 1 月至 2018 年 2 月期间至少 18 岁、患有 HR+/HER2-或 TNBC 且 mBC 诊断的美国患者进行了一项真实世界回顾性分析，评估 gBRCA 检测率。使用逆概率治疗加权法比较 gBRCAm HR+/HER2-与 TNBC 患者之间的结局差异；使用对数秩检验评估 HR+/HER2-与 TNBC 对总生存期（OS）的影响，总结抗肿瘤治疗，并使用 t 检验分析 HRU。
结果：该研究纳入了 12021 例 mBC 患者（HR+/HER2-，10291 例；TNBC，1730 例）。2005 例（16.7%）患者的 gBRCA 检测结果可供分析（HR+/HER2-，1587 例；TNBC，418 例）。共有 229 例（1.9%）患者（HR+/HER2-，165 例；TNBC，64 例）存在 gBRCAm。在 gBRCAm mBC 患者中，TNBC 与 HR+/HER2-相比，OS 明显更差[风险比（95%置信区间），0.45（0.27-0.74）；p=0.002]。gBRCAm mBC 患者的估计中位和 4 年 OS 率分别为 38.0 个月、23.4 个月和 35.6%、21.2%。gBRCAm HR+/HER2-患者的一线治疗最常见的是来曲唑（8%），而 gBRCAm TNBC 患者则是卡培他滨（14%）。与 HR+/HER2-患者相比，gBRCAm mBC 患者每年每例患者的 HRU 治疗就诊次数明显更高（p<0.05）。
结论：在 HR-/HER2-mBC 患者中，gBRCA 检测率较低。在 gBRCAm HR-/HER2-mBC 患者中，观察到较差的 OS 和 HRU 负担，特别是在 TNBC 患者中，这表明需要更有效、更有针对性且 HRU 负担更小的治疗方案。
资金来源：辉瑞公司。
Breast Care (Basel). 2021-4
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