Chirila Costel, Mitra Debanjali, Colosia Ann, Ling Caroline, Odom Dawn, Iyer Shrividya, Kaye James A
a RTI Health Solutions , RTP , NC , USA.
b Pfizer Inc. , New York , NY , USA.
Curr Med Res Opin. 2017 Aug;33(8):1457-1466. doi: 10.1080/03007995.2017.1325730. Epub 2017 May 16.
Palbociclib is the first cyclin-dependent kinase 4/6 inhibitor approved in the United States for HR+/HER2- advanced/metastatic breast cancer, in combination with letrozole as initial endocrine-based therapy in postmenopausal women or with fulvestrant in women with disease progression following endocrine therapy. We compared progression-free survival (PFS) and discontinuations due to adverse events for palbociclib combinations against other endocrine therapies using a mixed-treatment comparison meta-analysis of randomized, controlled trials.
A systematic literature review identified relevant trials. Separate analyses were conducted for each palbociclib combination using a Bayesian approach. Treatment rankings were established using the surface under the cumulative ranking curve (SUCRA).
Sixty-five unique studies met inclusion criteria. Palbociclib plus letrozole had the highest SUCRA value (99.9%) and was associated with significantly longer PFS than all comparators in treatment-naïve patients (hazard ratios [HRs] ranged from 0.41 to 0.58). Palbociclib plus fulvestrant had the second highest SUCRA value (93.9%) and, in previously treated patients, yielded significantly longer PFS than most comparators (HRs ranged from 0.26 to 0.46); the exception was everolimus plus exemestane, with similar PFS (HR, 1.04; 95% credible interval [CrI], 0.58-1.76). Palbociclib plus fulvestrant was associated with significantly lower odds of discontinuation due to adverse events than everolimus plus exemestane (odds ratio, 0.14; 95% CrI, 0.05-0.39).
The results suggest that the two palbociclib combinations yielded significantly greater PFS than endocrine therapy in treatment-naïve and previously treated patients with advanced/metastatic breast cancer. Palbociclib plus fulvestrant was associated with significantly less toxicity than everolimus plus exemestane.
帕博西尼是美国批准的首个细胞周期蛋白依赖性激酶4/6抑制剂，用于激素受体阳性/人表皮生长因子受体2阴性的晚期/转移性乳腺癌，与来曲唑联合用于绝经后女性的初始内分泌治疗，或与氟维司群联合用于内分泌治疗后疾病进展的女性。我们使用随机对照试验的混合治疗比较荟萃分析，比较了帕博西尼联合用药与其他内分泌治疗的无进展生存期（PFS）以及因不良事件导致的停药情况。
系统的文献综述确定了相关试验。使用贝叶斯方法对每种帕博西尼联合用药进行单独分析。使用累积排名曲线下面积（SUCRA）建立治疗排名。
65项独特研究符合纳入标准。帕博西尼加来曲唑的SUCRA值最高（99.9%），与初治患者中所有对照相比，其PFS显著更长（风险比[HRs]范围为0.41至0.58）。帕博西尼加氟维司群的SUCRA值第二高（93.9%），在既往接受过治疗的患者中，其PFS显著长于大多数对照（HRs范围为0.26至0.46）；依维莫司加依西美坦除外，二者PFS相似（HR，1.04；95%可信区间[CrI]，0.58 - 1.76）。与依维莫司加依西美坦相比，帕博西尼加氟维司群因不良事件导致停药的几率显著更低（优势比，0.14；95% CrI，0.05 - 0.39）。
结果表明，在初治和既往接受过治疗的晚期/转移性乳腺癌患者中，两种帕博西尼联合用药的PFS显著长于内分泌治疗。与依维莫司加依西美坦相比，帕博西尼加氟维司群的毒性显著更低。
