Cornerstone Research Group Inc., Suite 204, 3228 South Service Road, Burlington, ON, L7N 3H8, Canada.
Pfizer, Inc., New York, NY, USA.
Breast Cancer Res Treat. 2017 Nov;166(1):167-177. doi: 10.1007/s10549-017-4404-4. Epub 2017 Jul 27.
To compare palbociclib + letrozole and palbociclib + fulvestrant with chemotherapy agents in postmenopausal women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced/metastatic breast cancer (ABC/MBC) who had no prior systemic treatment for advanced disease (first line) or whose disease progressed after prior endocrine therapy or chemotherapy (second line).
A systematic search identified randomized controlled trials (RCTs) published from January 2000 to January 2016 that compared endocrine-based therapies, chemotherapy agents, and/or chemotherapy agents + biological therapies in the first- and second-line treatment of postmenopausal women with HR+/HER2- ABC/MBC. The main outcome of interest was progression-free survival (PFS)/time to progression (TTP). Bayesian network meta-analyses (NMAs) and pairwise meta-analyses were conducted. Heterogeneity and inconsistency were assessed.
Sixty RCTs met eligibility criteria and were stratified by line of therapy. In the first line, palbociclib + letrozole showed statistically significant improvements in PFS/TTP versus capecitabine [intermittent: HR 0.28 (95% CrI 0.11-0.72)] and mitoxantrone [HR 0.28 (0.13-0.61)], and trended toward improvements versus paclitaxel [HR 0.59 (0.19-1.96)], docetaxel [HR 0.51 (0.14-2.03)] and other monotherapy or combination agents (HRs ranging from 0.24 to 0.99). In the second line, palbociclib + fulvestrant showed statistically significant improvements in PFS/TTP versus capecitabine [intermittent: HR 0.28 (0.13-0.65)], mitoxantrone [HR 0.26 (0.12-0.53)], and pegylated liposomal doxorubicin [HR 0.19 (0.07-0.50)], and trended toward improvements versus paclitaxel [HR 0.48 (0.16-1.44)], docetaxel [HR 0.71 (0.24-2.13)] and other monotherapy or combination agents (HRs ranging from 0.23-0.89). NMA findings aligned with direct evidence and were robust to sensitivity analyses.
Palbociclib + letrozole and palbociclib + fulvestrant demonstrate trends in incremental efficacy compared with chemotherapy agents for the first- and second-line treatment of HR +/HER2- ABC/MBC.
比较帕博西尼联合来曲唑和帕博西尼联合氟维司群与化疗药物在激素受体阳性（HR+）/人表皮生长因子受体 2 阴性（HER2-）的绝经后晚期/转移性乳腺癌（ABC/MBC）患者中的疗效，这些患者在晚期疾病的一线治疗中没有接受过系统治疗，或在接受内分泌治疗或化疗后疾病进展。
系统检索 2000 年 1 月至 2016 年 1 月期间发表的随机对照试验（RCTs），比较了在 HR+/HER2-ABC/MBC 的一线和二线治疗中，基于内分泌的治疗、化疗药物以及/或化疗药物联合生物治疗的效果。主要研究终点为无进展生存期（PFS）/疾病进展时间（TTP）。采用贝叶斯网络荟萃分析（NMAs）和成对荟萃分析。评估了异质性和不一致性。
符合纳入标准的 60 项 RCT 按治疗线进行分层。在一线治疗中，与卡培他滨[间歇治疗：HR0.28（95%CrI0.11-0.72）]和米托蒽醌[HR0.28（0.13-0.61）]相比，帕博西尼联合来曲唑在 PFS/TTP 方面显示出统计学意义上的显著改善，且与紫杉醇[HR0.59（0.19-1.96）]、多西他赛[HR0.51（0.14-2.03）]和其他单药或联合用药（HR 范围为 0.24-0.99）的趋势一致。在二线治疗中，与卡培他滨[间歇治疗：HR0.28（0.13-0.65）]、米托蒽醌[HR0.26（0.12-0.53）]和聚乙二醇脂质体阿霉素[HR0.19（0.07-0.50）]相比，帕博西尼联合氟维司群在 PFS/TTP 方面显示出统计学意义上的显著改善，且与紫杉醇[HR0.48（0.16-1.44）]、多西他赛[HR0.71（0.24-2.13）]和其他单药或联合用药（HR 范围为 0.23-0.89）的趋势一致。NMA 结果与直接证据一致，且对敏感性分析具有稳健性。
帕博西尼联合来曲唑和帕博西尼联合氟维司群在 HR+/HER2-ABC/MBC 的一线和二线治疗中，与化疗药物相比，显示出了趋势性的疗效改善。
