一项多中心、随机、双盲、二期研究，旨在评估依维莫司诱导剂量递增在转移性乳腺癌患者中的耐受性（DESIREE）。
A multicentre, randomised, double-blind, phase II study to evaluate the tolerability of an induction dose escalation of everolimus in patients with metastatic breast cancer (DESIREE).
机构信息
Universitätsmedizin Mainz, Mainz, Germany.
Diakovere Henriettenstift Hannover, Hanover, Germany.
出版信息
ESMO Open. 2022 Dec;7(6):100601. doi: 10.1016/j.esmoop.2022.100601. Epub 2022 Nov 7.
BACKGROUND
Stomatitis is one of the main reasons to discontinue everolimus in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC). To decrease stomatitis and subsequently early treatment discontinuations or dose reductions, the DESIREE trial investigated the use of a stepwise dose-escalation schedule of everolimus (EVE esc).
PATIENTS AND METHODS
DESIREE is a phase II, multicentre, randomised, double-blind, placebo-controlled trial in patients with HR+/HER2- mBC and progression/relapse after nonsteroidal aromatase inhibitor treatment. Patients were randomised to EVE esc (2.5 mg/day, week 1; 5 mg/day, week 2; 7.5 mg/day, week 3; 10 mg/day, weeks 4-24) or everolimus 10 mg/day (EVE 10mg) for 24 weeks plus exemestane. The primary endpoint was the incidence of stomatitis episodes grade ≥2 within 12 weeks of treatment. The secondary endpoints included toxicity, relative total dose intensity (RTDI) and quality of life (QoL).
RESULTS
A total of 160 patients were randomised and 156 started treatment (EVE esc: 80; EVE 10mg: 76). The median age of patients was 64 years (range 33-85), 56.3% patients in the EVE esc arm versus 42.1% in the EVE 10mg arm had liver metastasis (P = 0.081) and 62.5% versus 51.3% received over one metastatic therapy line (P = 0.196). Within 12 weeks, the incidence of stomatitis episodes grade ≥2 was significantly lower in the EVE esc arm compared with the EVE 10mg arm (28.8% versus 46.1%; odds ratio 0.47, 95% confidence interval 0.24-0.92; P = 0.026). Toxicity was in line with the known safety profile without new safety concerns. The median RTDI was 91.1% in the EVE esc arm versus 80.0% in the EVE 10mg arm (P = 0.329). Discontinuation rate in the first 3 weeks was 6.3% versus 15.8%, respectively (P = 0.073). QoL was comparable between the two treatment arms.
CONCLUSIONS
A dose-escalation schema of everolimus over 3 weeks can be successfully used to reduce the incidence of high-grade stomatitis in the first 12 weeks of treatment in patients with HR+/HER2- mBC.
TRIAL REGISTRATION
ClinicalTrials.govNCT02387099; https://clinicaltrials.gov/ct2/show/NCT02387099.
背景
口腔炎是导致激素受体阳性（HR+）/人表皮生长因子受体 2 阴性（HER2-）转移性乳腺癌（mBC）患者停止使用依维莫司的主要原因之一。为了减少口腔炎并随后减少早期治疗中断或剂量减少，DESIREE 试验研究了依维莫司（EVE）逐步递增剂量方案的使用。
患者和方法
DESIREE 是一项 II 期、多中心、随机、双盲、安慰剂对照试验，入组 HR+/HER2-mBC 患者，这些患者在非甾体芳香酶抑制剂治疗后出现进展/复发。患者被随机分配至 EVE esc（2.5mg/天，第 1 周；5mg/天，第 2 周；7.5mg/天，第 3 周；10mg/天，第 4-24 周）或依维莫司 10mg/天（EVE 10mg）治疗 24 周加依西美坦。主要终点是治疗后 12 周内≥2 级口腔炎发作的发生率。次要终点包括毒性、相对总剂量强度（RTDI）和生活质量（QoL）。
结果
共随机分配了 160 名患者，其中 156 名患者开始治疗（EVE esc：80 名；EVE 10mg：76 名）。患者的中位年龄为 64 岁（范围 33-85 岁），EVE esc 臂中 56.3%的患者与 EVE 10mg 臂中 42.1%的患者有肝转移（P=0.081），62.5%与 51.3%的患者接受了超过一线转移性治疗（P=0.196）。在 12 周内，EVE esc 臂中≥2 级口腔炎发作的发生率明显低于 EVE 10mg 臂（28.8%与 46.1%；比值比 0.47，95%置信区间 0.24-0.92；P=0.026）。毒性与已知的安全性特征一致，无新的安全性问题。EVE esc 臂的中位 RTDI 为 91.1%，EVE 10mg 臂为 80.0%（P=0.329）。在前 3 周的停药率分别为 6.3%与 15.8%（P=0.073）。两个治疗臂的生活质量相当。
结论
依维莫司的剂量递增方案在 3 周内可成功用于降低 HR+/HER2-mBC 患者前 12 周治疗中≥2 级口腔炎的发生率。
试验注册
ClinicalTrials.govNCT02387099；https://clinicaltrials.gov/ct2/show/NCT02387099。
Zotero 插件