Background: The BALLET study was an open-label, multicenter, expanded access study designed to allow treatment with everolimus plus exemestane in postmenopausal women with hormone receptor-positive metastatic breast cancer progressed following prior endocrine therapy. A post hoc analysis to evaluate if previous chemotherapy in the metastatic setting affects the safety profile of the combination regimen of everolimus and exemestane was conducted on the Italian subset, as it represented the major part of the patients enrolled (54%).
Patients and methods: One thousand one hundred and fifty-one Italian patients were included in the present post hoc analysis, which focused on two sets of patients: patients who never received chemotherapy in the metastatic setting (36.1%) and patients who received at least one chemotherapy treatment in the metastatic setting (63.9%).
Results: One thousand one hundred and sixteen patients (97.0%) prematurely discontinued the study drug, and the main reasons reported were disease progression (39.1%), local reimbursement of everolimus (31.1%), and adverse events (AEs) (16.1%). The median duration of study treatment exposure was 139.5 days for exemestane and 135.0 days for everolimus. At least one AE was experienced by 92.5% of patients. The incidence of everolimus-related AEs was higher (83.9%) when compared with those that occurred with exemestane (29.1%), and the most commonly reported everolimus-related AE was stomatitis (51.3%). However, no significant difference in terms of safety related to the combination occurred between patients without and with chemotherapy in the metastatic setting.
Conclusion: Real-life data of the Italian patients BALLET-related cohort were an adequate setting to state that previous chemotherapy did not affect the safety profile of the combination regimen of everolimus and exemestane.
Implications for practice: With the advent of new targeted agents for advanced or metastatic breast cancer, multiple lines of therapy may be possible, and components of the combined regimens can overlap from one line to another. Thus, it is important to assess even the potential of cumulative and additive toxic effects among the drugs. Previous chemotherapy did not affect the safety profile of the combination regimen of everolimus and exemestane. The continuous monitoring of the safety signals of this drug combination from general clinical practice is important, in particular for stomatitis.
摘要
背景. BALLET研究是一项开放性、多中心、扩大供药研究, 患有激素受体阳性转移性乳腺癌且既往内分泌治疗后疾病进展的绝经后女性可在研究中接受依维莫司和依西美坦联合治疗。入组患者大部分为意大利人（54%）, 因此在意大利患者子集中进行了一项事后分析, 以评价既往在疾病转移后接受化疗是否会影响依维莫司和依西美坦联合治疗方案的安全性特征。
患者和方法. 本项事后分析纳入了1 151例意大利患者, 重点分析两组患者：从未接受过化疗的转移性乳腺癌患者（36.1%）和至少接受过一次化疗的转移性乳腺癌患者（63.9%）。
结果. 1 116例患者（97.0%）提前停用研究药物, 报告的主要原因为疾病进展（39.1%）、当地报销依维莫司（31.1%）和不良事件（AE；16.1%）。依西美坦和依维莫司的研究治疗中位持续时间分别为139.5天和135.0天。92.5%的患者至少发生1例AE。依维莫司（83.9%）相关AE的发生率高于依西美坦（29.1%）, 最常报告的依维莫司相关AE为口腔炎（51.3%）。然而, 接受和未接受化疗的转移性乳腺癌患者在联合治疗的相关安全性方面没有显著差异。
结论. BALLET研究中意大利患者队列的实际数据充分说明, 既往化疗不影响依维莫司和依西美坦联合治疗方案的安全性特征。The Oncologist 2017;22:648–654
对临床实践的提示：晚期或转移性乳腺癌的新靶向药物问世后, 患者或许可以接受多线治疗, 而各线联合治疗方案中的药物可能相互重叠。因此, 评估药物毒性作用的潜在累积和叠加风险至关重要。既往化疗不影响依维莫司和依西美坦联合治疗方案的安全性特征。在一般临床实践中必须持续监测这一联合用药的安全性信号, 特别是口腔炎。
Keywords: Advanced breast cancer; Everolimus; Hormone‐receptor positive; Real life; Safety.
© AlphaMed Press 2017.