Lessons learned: Single-agent selinexor has limited activity in heavily pretreated patients with metastatic triple-negative breast cancer.Selinexor 60 mg by mouth twice weekly was generally well tolerated with a side-effect profile consistent with previous clinical trials.Future studies of selinexor in this population should focus on combination approaches and a biomarker-driven strategy to identify patients most likely to benefit.
Background: This phase II trial evaluated the safety, pharmacodynamics, and efficacy of selinexor (KPT-330), an oral selective inhibitor of nuclear export (SINE) in patients with advanced triple-negative breast cancer (TNBC).
Methods: This phase II trial was designed to enroll 30 patients with metastatic TNBC. Selinexor was given at 60 mg orally twice weekly on days 1 and 3 of each week, three of each 4-week cycle. The primary objective of this study was to determine the clinical benefit rate (CBR), defined as complete response + partial response + stable disease (SD) ≥12 weeks.
Results: Ten patients with a median age of 60 years (range 44-71 years) were enrolled between July 2015 and January 2016. The median number of prior chemotherapy lines was 2 (range 1-5). A planned interim analysis for the first stage per protocol was performed. Three patients had SD and seven had progressive disease. On the basis of these results and predefined stoppage rules, the study was halted.
Conclusion: Selinexor was fairly well tolerated in patients with advanced TNBC but did not result in objective responses. However, clinical benefit rate was 30%, and further investigation of selinexor in this patient population should focus on combination therapies.
经验获取
对于既往接受多次治疗的转移性三阴性乳腺癌患者，单剂 Selinexor 的活性有限。
Selinexor 60mg口服，每周两次，总体耐受良好，副作用与先前临床试验结果一致。
未来针对 Selinexor 对于这类患者的研究应侧重于联合用药和以生物标志物为驱动的策略，确定最有可能从中受益的患者。
摘要
背景。本 II 期试验评估了口服选择性核输出抑制剂(SINE) Selinexor (KPT‐330) 在晚期三阴性乳腺癌 (TNBC) 患者治疗中的安全性、药效和有效性。
方法。本 II 期试验计划入组 30 例转移性 TNBC 患者。Selinexor 60mg口服，每周第 1 天和第 3 天共服用 2 次，服用 3 周，疗程为 4 周。本研究的主要目的是确定临床获益率 (CBR)，具体定义为 ≥12 周的完全缓解率 + 部分缓解率 + 病情稳定率 (SD))。
结果。于 2015 年 7 月至 2016 年 1 月入组 10 例患者，中位年龄为 60 岁(范围为 44‐71 岁)。既往中位化疗线数为 2 (范围为 1‐5 )。根据方案对第一阶段进行计划期中分析。三名患者出现 SD，七名患者出现疾病进展。根据这些结果和预先确定的中止规则，停止了研究。
结论。晚期 TNBC 患者对 Selinexor 的耐受性较好，但没有引起客观缓解。临床获益率为 30%，对这类患者群体使用 Selinexor 的进一步研究应侧重于联合治疗。
Trial registration: ClinicalTrials.gov NCT02402764.
© AlphaMed Press; the data published online to support this summary are the property of the authors.