Analysis Group, Inc, Boston, Massachusetts.
Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.
Clin Ther. 2018 Apr;40(4):628-639.e3. doi: 10.1016/j.clinthera.2018.03.004. Epub 2018 Mar 31.
The comparative efficacy of endocrine-based therapies (ETs) for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (mBC) is not well characterized. This network meta-analysis (NMA) synthesized available evidence on progression-free survival (PFS) with first-line ETs for postmenopausal HR+/HER2- mBC.
A systematic literature review identified randomized controlled trials of first-line ETs. Pairwise hazard ratios and 95% credible intervals (CrIs) were obtained via a Bayesian NMA model. Subgroup NMAs were conducted among late progressors (disease-free interval ≥12 months from completion of [neo] adjuvant therapy with letrozole or anastrozole at the time of randomization) and de novo patients, defined as patients whose initial BC diagnosis is mBC.
Five trials and 5 regimens (ribociclib + an aromatase inhibitor [AI] [LEE + AI], palbociclib + AI [Pal + AI], fulvestrant 250 mg + AI [Ful250 + AI], fulvestrant 500 mg [Ful500], and AI) were selected. LEE + AI, Pal + AI, Ful250 + AI, and Ful500 had significantly longer PFS versus AI (95% CrI upper-bound ≤1). LEE + AI had a 30% and 29%, and Pal + AI had a 31% and 30%, reduced hazard of progression or death versus Ful250 + AI and Ful500 (95% CrI upper-bound ≤1), respectively. The probability of being the most efficacious was 46% for LEE + AI and 54% for Pal + AI. In subgroup analyses among late progressors, LEE + AI had a 4% reduced hazard of progression or death versus Pal + AI but was not statistically significant. In the de novo analysis, Pal + AI and LEE + AI had a 29% and 40% reduced hazard of progression or death versus Ful500, respectively, but were not statistically significant. In both subgroup analyses, all therapies had significantly longer PFS compared with AI.
Pal + AI, LEE + AI, Ful250 + AI, or Ful500 as first-line treatment for HR+/HER2- mBC had longer PFS than AI alone. Given the lack of head-to-head clinical trials comparing the efficacy of recently approved first-line ETs for HR+/HER2- mBC, these results have important clinical implications for the treatment of HR+/HER2- mBC in the first-line setting.
激素受体阳性/人表皮生长因子受体 2 阴性（HR+/HER2-）转移性乳腺癌（mBC）的内分泌治疗（ET）的比较疗效尚不清楚。本网络荟萃分析（NMA）综合了用于绝经后 HR+/HER2-mBC 的一线 ET 治疗的无进展生存期（PFS）的现有证据。
系统文献检索确定了一线 ET 的随机对照试验。通过贝叶斯 NMA 模型获得了成对风险比和 95%可信区间（CrI）。在晚期进展者（从完成来曲唑或阿那曲唑的[新]辅助治疗到随机分组时的疾病无进展间隔≥12 个月）和新诊断患者（最初的 BC 诊断为 mBC 的患者）中进行了亚组 NMA。
纳入了 5 项试验和 5 种方案（ribociclib+芳香化酶抑制剂[AI] [LEE+AI]、palbociclib+AI [Pal+AI]、氟维司群 250mg+AI [Ful250+AI]、氟维司群 500mg [Ful500]和 AI）。与 AI 相比，LEE+AI、Pal+AI、Ful250+AI 和 Ful500 具有显著更长的 PFS（95%CrI 上限≤1）。与 Ful250+AI 和 Ful500 相比，LEE+AI 和 Pal+AI 进展或死亡的风险分别降低了 30%和 29%和 31%和 30%（95%CrI 上限≤1）。LEE+AI 和 Pal+AI 的最有效概率分别为 46%和 54%。在晚期进展者的亚组分析中，与 Pal+AI 相比，LEE+AI 进展或死亡的风险降低了 4%，但无统计学意义。在新诊断分析中，Pal+AI 和 LEE+AI 与 Ful500 相比，进展或死亡的风险分别降低了 29%和 40%，但无统计学意义。在这两个亚组分析中，与 AI 相比，所有治疗方案的 PFS 均显著延长。
在 HR+/HER2-mBC 中，与 AI 相比，Pal+AI、LEE+AI、Ful250+AI 或 Ful500 作为一线治疗具有更长的 PFS。鉴于最近批准的用于 HR+/HER2-mBC 的一线 ET 疗效比较的头对头临床试验缺乏，这些结果对 HR+/HER2-mBC 一线治疗具有重要的临床意义。
