Cancer Care Centre, St George Hospital, Sydney, NSW, Australia.
National Health and Medical Research Council (NHMRC) Clinical Trials Centre, University of Sydney, Locked Bag 77, Camperdown, NSW, 1450, Australia.
Breast Cancer Res Treat. 2019 Feb;174(1):271-278. doi: 10.1007/s10549-018-5054-x. Epub 2018 Nov 21.
Adding cyclin-dependent kinase (CDK) 4/6 inhibitor to endocrine therapy improves progression-free survival (PFS) in advanced breast cancer but the impact of ethnicity on efficacy and toxicity is unclear. We aimed to estimate the relative treatment efficacy and toxicity of endocrine therapy with and without CDK4/6 inhibitors, and compare between Asian/non-Asian subgroups.
This meta-analysis included published first-line randomized trials comparing CDK4/6 inhibitor-endocrine therapy versus endocrine monotherapy. Hazard ratios (HR) and 95% confidence intervals (CI) for the overall population and Asian/non-Asian subgroups were extracted. The inverse-variance-weighted method was used to pool treatment estimates of PFS.
Four trials (N = 2499) were included. Patients received combination CDK4/6 inhibitor-endocrine therapy (N = 1441; ribociclib, [46.4%]; palbociclib, [30.8%]; or abemaciclib, [22.8%]) versus endocrine monotherapy (N = 1058). CDK4/6 inhibitor-endocrine therapy was associated with prolonged PFS compared with endocrine monotherapy (HR 0.56; 95% CI 0.50-0.62). In Asians (N = 492), PFS HR was 0.39 (95% CI 0.29-0.51, P < 0.0001). In non-Asians (N = 2007), PFS HR was 0.62 (95% CI 0.54-0.71, P < 0.0001). There was a significant treatment-by-ethnicity interaction (P = 0.002). Toxicity data by ethnic subgroup were only available from two trials (n = 1334) with no convincing evidence that the risk of toxicity between CDK4/6 inhibitor-endocrine therapy and endocrine monotherapy varied by ethnicity.
Adding CDK4/6 inhibitor to endocrine therapy prolongs PFS compared to endocrine therapy alone as first-line treatment in advanced breast cancer. The magnitude of PFS benefit is ethnicity-dependent but there is no interethnic differences in relative treatment-related toxicities. These findings may assist in the design and interpretation of trials, inform economic analyses, and stimulate pharmacogenomic research.
在晚期乳腺癌中，添加细胞周期蛋白依赖性激酶（CDK）4/6 抑制剂联合内分泌治疗可改善无进展生存期（PFS），但种族对疗效和毒性的影响尚不清楚。本研究旨在评估内分泌治疗联合和不联合 CDK4/6 抑制剂的相对治疗效果和毒性，并比较亚洲/非亚洲亚组之间的差异。
本荟萃分析纳入了已发表的比较 CDK4/6 抑制剂联合内分泌治疗与内分泌单药治疗作为一线治疗的随机试验。提取总体人群和亚洲/非亚洲亚组的风险比（HR）和 95%置信区间（CI）。采用倒数方差加权法对 PFS 的治疗估计值进行汇总。
共纳入四项试验（N=2499 例）。患者接受联合 CDK4/6 抑制剂-内分泌治疗（N=1441 例；瑞博西利，[46.4%]；哌柏西利，[30.8%]；或阿贝西利，[22.8%]）与内分泌单药治疗（N=1058 例）。与内分泌单药治疗相比，CDK4/6 抑制剂联合内分泌治疗可延长 PFS（HR 0.56；95%CI 0.50-0.62）。在亚洲人群（N=492 例）中，PFS HR 为 0.39（95%CI 0.29-0.51，P<0.0001）。在非亚洲人群（N=2007 例）中，PFS HR 为 0.62（95%CI 0.54-0.71，P<0.0001）。存在治疗与种族的显著交互作用（P=0.002）。两个试验（n=1334 例）提供了按种族亚组划分的毒性数据，但没有令人信服的证据表明 CDK4/6 抑制剂联合内分泌治疗与内分泌单药治疗的毒性风险存在种族差异。
与内分泌单药治疗作为晚期乳腺癌的一线治疗相比，添加 CDK4/6 抑制剂可显著延长 PFS。PFS 获益的程度与种族有关，但种族间的相对治疗相关毒性无差异。这些发现可能有助于试验设计和解释，为经济分析提供信息，并激发药物基因组学研究。
