内脏转移对绝经后晚期乳腺癌患者依维莫司疗效和安全性的影响：BOLERO-2 研究的亚组分析。
Effect of visceral metastases on the efficacy and safety of everolimus in postmenopausal women with advanced breast cancer: subgroup analysis from the BOLERO-2 study.
机构信息
Institut de Cancérologie de l'Ouest-René Gauducheau, Centre de Recherche en Cancérologie, Boulevard Jacques Monod, 44805 Saint Herblain-Nantes cedex, France.
出版信息
Eur J Cancer. 2013 Aug;49(12):2621-32. doi: 10.1016/j.ejca.2013.04.011. Epub 2013 Jun 1.
BACKGROUND
Everolimus (EVE; an inhibitor of mammalian target of rapamycin [mTOR]) enhances treatment options for postmenopausal women with hormone-receptor-positive (HR(+)), human epidermal growth factor receptor-2-negative (HER2(-)) advanced breast cancer (ABC) who progress on a non-steroidal aromatase inhibitor (NSAI). This is especially true for patients with visceral disease, which is associated with poor prognosis. The BOLERO-2 (Breast cancer trial of OraLEveROlimus-2) trial showed that combination treatment with EVE and exemestane (EXE) versus placebo (PBO)+EXE prolonged progression-free survival (PFS) by both investigator (7.8 versus 3.2 months, respectively) and independent (11.0 versus 4.1 months, respectively) central assessment in postmenopausal women with HR(+), HER2(-) ABC recurring/progressing during/after NSAI therapy. The BOLERO-2 trial included a substantial proportion of patients with visceral metastases (56%).
METHODS
Prespecified exploratory subgroup analysis conducted to evaluate the efficacy and safety of EVE+EXE versus PBO+EXE in a prospectively defined subgroup of patients with visceral metastases.
FINDINGS
At a median follow-up of 18 months, EVE+EXE significantly prolonged median PFS compared with PBO+EXE both in patients with visceral metastases (N=406; 6.8 versus 2.8 months) and in those without visceral metastases (N=318; 9.9 versus 4.2 months). Improvements in PFS with EVE+EXE versus PBO+EXE were also observed in patients with visceral metastases regardless of Eastern Cooperative Oncology Group performance status (ECOG PS). Patients with visceral metastases and ECOG PS 0 had a median PFS of 6.8 months with EVE+EXE versus 2.8 months with PBO+EXE. Among patients with visceral metastases and ECOG PS ≥1, EVE+EXE treatment more than tripled median PFS compared with PBO+EXE (6.8 versus 1.5 months).
INTERPRETATION
Adding EVE to EXE markedly extended PFS by ≥4 months among patients with HR(+) HER2(-) ABC regardless of the presence of visceral metastases.
背景
依维莫司（EVE；哺乳动物雷帕霉素靶蛋白[mTOR]抑制剂）可增强绝经后激素受体阳性（HR(+））、人表皮生长因子受体 2 阴性（HER2(-））晚期乳腺癌（ABC）患者的治疗选择，这些患者在非甾体芳香酶抑制剂（NSAI）治疗后进展。对于有内脏疾病的患者尤其如此，因为这与预后不良有关。BOLERO-2（乳腺癌试验的奥拉莫唑罗利姆-2）试验表明，与安慰剂（PBO）+EXE 相比，EVE 和依西美坦（EXE）联合治疗可分别通过研究者（分别为 7.8 个月和 3.2 个月）和独立中心评估（分别为 11.0 个月和 4.1 个月）延长 HR(+）、HER2(-）ABC 复发/进展患者的无进展生存期（PFS），这些患者在 NSAI 治疗期间/之后发生进展。BOLERO-2 试验纳入了相当比例的有内脏转移的患者（56%）。
方法
进行了预先指定的探索性亚组分析，以评估在有内脏转移的患者中，EVE+EXE 与 PBO+EXE 的疗效和安全性。
结果
在中位随访 18 个月时，与 PBO+EXE 相比，EVE+EXE 可显著延长有内脏转移的患者（N=406；6.8 个月比 2.8 个月）和无内脏转移的患者（N=318；9.9 个月比 4.2 个月）的中位 PFS。EVE+EXE 与 PBO+EXE 相比，无论东部肿瘤协作组表现状态（ECOG PS）如何，有内脏转移的患者的 PFS 也有改善。有内脏转移且 ECOG PS 为 0 的患者中，EVE+EXE 治疗的中位 PFS 为 6.8 个月，而 PBO+EXE 为 2.8 个月。对于有内脏转移且 ECOG PS≥1 的患者，EVE+EXE 治疗使中位 PFS 延长了两倍多，而 PBO+EXE 为 1.5 个月。
解释
在 HR(+）HER2(-）ABC 患者中，无论是否有内脏转移，添加 EVE 均可使 EXE 的 PFS 延长≥4 个月。
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