Robert H Lurie Comprehensive Cancer Center, Feinberg School of Medicine, 710 N Fairbanks Ct, Ste 8-250A, Chicago, IL 60611, USA.
University of Pennsylvania Abramson Cancer Center, 3400 Civic Center Boulevard, Philadelphia, PA 19104, USA.
Eur J Cancer. 2018 Nov;104:21-31. doi: 10.1016/j.ejca.2018.08.011. Epub 2018 Oct 8.
The addition of palbociclib to fulvestrant improved clinical outcomes over placebo-fulvestrant in endocrine-pretreated metastatic breast cancer (MBC) patients in PALOMA-3. Here, we examined factors predictive of long-term benefit.
Premenopausal-peri/postmenopausal patients with endocrine-resistant, hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative MBC were randomised 2:1 to fulvestrant (500 mg) and either palbociclib (125 mg/d; 3/1 schedule; n = 347) or placebo (n = 174). Baseline characteristics, mutation status and HR expression levels were compared in patients with and without prolonged benefit (treatment duration ≥18 months).
By August 2016, 100 patients (29%) on palbociclib-fulvestrant and 26 (15%) on placebo-fulvestrant demonstrated prolonged benefit, with long-term responders in both arms sharing common clinical characteristics. They usually had less disease burden at baseline versus those treated <18 months, such as having one disease site (40% vs 29% on palbociclib-fulvestrant and 69% vs 29% on placebo-fulvestrant), bone-only disease (32% vs 22% and 46% vs 17%) and were less heavily pretreated (69% vs 56% and 73% vs 60% had ≤2 prior therapies). Baseline tumour ESR1 and PIK3CA mutation rates were lower among long-term responders in both arms; median oestrogen receptor H-scores were similar, whereas progesterone receptor H-scores were higher among long-term responders.
This exploratory analysis demonstrates that some patients with endocrine-resistant MBC derive significant and prolonged benefit when treated with palbociclib-fulvestrant, with fewer patients experiencing similar efficacy with placebo-fulvestrant. The current analysis did not identify specific molecular or clinical factors prognostic of long-term benefit with palbociclib-fulvestrant (ClinicalTrials.gov, NCT01942135).
在 PALOMA-3 试验中，帕博西尼联合氟维司群相较于安慰剂联合氟维司群，在内分泌治疗失败的转移性乳腺癌（MBC）患者中改善了临床结局。在此，我们研究了长期获益的预测因素。
对于内分泌耐药、激素受体阳性（HR+）/人表皮生长因子受体 2 阴性的 MBC 患者，按照 2:1 的比例随机分配至氟维司群（500mg）+帕博西尼（125mg/d；3/1 方案）组（n=347）或氟维司群+安慰剂组（n=174）。比较有和无长期获益（治疗持续时间≥18 个月）患者的基线特征、突变状态和 HR 表达水平。
截至 2016 年 8 月，帕博西尼+氟维司群组 100 例患者（29%）和安慰剂+氟维司群组 26 例患者（15%）显示出长期获益，两个治疗组的长期应答者具有共同的临床特征。与治疗时间<18 个月的患者相比，他们通常具有更少的基线疾病负担，例如仅一个疾病部位（帕博西尼+氟维司群组 40% vs 29%和安慰剂+氟维司群组 69% vs 29%）、骨转移（32% vs 22%和 46% vs 17%）和较少的既往治疗（69% vs 56%和 73% vs 60%接受≤2 种治疗方案）。在两个治疗组中，长期应答者的基线肿瘤 ESR1 和 PIK3CA 突变率较低；中位雌激素受体 H 评分相似，而孕激素受体 H 评分较高。
这项探索性分析表明，一些内分泌耐药的 MBC 患者接受帕博西尼+氟维司群治疗可获得显著且持久的获益，而安慰剂+氟维司群组中具有相似疗效的患者较少。目前的分析并未确定帕博西尼+氟维司群组长期获益的特定分子或临床因素（ClinicalTrials.gov，NCT01942135）。
