来曲唑或依西美坦联合或不联合 palbociclib 治疗进展后的 HR+/HER2-转移性乳腺癌的 TREnd 试验
Palbociclib as single agent or in combination with the endocrine therapy received before disease progression for estrogen receptor-positive, HER2-negative metastatic breast cancer: TREnd trial.
机构信息
"Sandro Pitigliani" Medical Oncology Department, Hospital of Prato, Prato, Italy.
Division of Early Drug Development, Department of Haematology and Haemato-Oncology, Istituto Europeo di Oncologia, University of Milan, Milan, Italy.
出版信息
Ann Oncol. 2018 Aug 1;29(8):1748-1754. doi: 10.1093/annonc/mdy214.
BACKGROUND
The activity of palbociclib as a single agent in advanced breast cancer has not been extensively studied, with the only available clinical data limited to heavily pretreated patients. Preclinical data suggests palbociclib may partially reverse endocrine resistance, though this hypothesis has not been evaluated in previous clinical studies. This phase II, open-label, multicenter study examined the activity of palbociclib monotherapy, as well as palbociclib given in combination with the same endocrine therapy (ET) that was received prior to disease progression, in postmenopausal women with moderately pretreated, estrogen receptor-positive, HER2 negative advanced breast cancer.
PATIENTS AND METHODS
Eligible women with advanced disease which had progressed on one or two prior ETs were randomized 1 : 1 to receive either palbociclib alone, or palbociclib in combination with the ET as previously received. Primary end point was clinical benefit rate (CBR); secondary end points included progression-free survival (PFS).
RESULTS
Between October 2012 and July 2016, a total of 115 patients were randomized. The CBR was 54% [95% confidence interval (CI): 41.5-63.7] for combination therapy, and 60% (95% CI: 47.8-72.9) for monotherapy. Median PFS was 10.8 months (95% CI: 5.6-12.7) for combination therapy, and 6.5 months (95% CI: 5.4-8.5) for monotherapy [hazard ratio (HR) 0.69; 95% CI: 0.4-1.1, exploratory P-value = 0.12]. Exploratory analyses revealed the PFS advantage for combination therapy was seen in the subgroup of patients who received prior ET for >6 months (HR 0.53; 95% CI: 0.3-0.9, exploratory P-value = 0.02), but not in those who received prior ET for ≤6 months.
CONCLUSION
Palbociclib has clinical activity as a single agent in women with moderately pretreated, oestrogen receptor-positive, HER2-negative advanced breast cancer. Palbociclib may have potential to reverse endocrine resistance in patients with a history of previous durable response to ET.
CLINICAL TRIAL INFORMATION
NCT02549430.
背景
帕博西尼单药治疗晚期乳腺癌的活性尚未得到广泛研究，唯一可用的临床数据仅限于经过大量预处理的患者。临床前数据表明，帕博西尼可能部分逆转内分泌耐药，但这一假设尚未在前瞻性临床研究中得到评估。本Ⅱ期、开放标签、多中心研究评估了帕博西利单药治疗以及帕博西利联合在疾病进展前接受的相同内分泌治疗（ET）在经过适度预处理的绝经后妇女中的活性，这些妇女患有雌激素受体阳性、HER2 阴性的晚期乳腺癌。
患者和方法
进展期疾病患者既往接受过一次或两次 ET 治疗，随机分为 1:1 接受帕博西利单药治疗或帕博西利联合先前接受的 ET 治疗。主要终点是临床获益率（CBR）；次要终点包括无进展生存期（PFS）。
结果
2012 年 10 月至 2016 年 7 月，共有 115 例患者被随机分组。联合治疗组的 CBR 为 54%（95%可信区间：41.5-63.7），单药治疗组为 60%（95%可信区间：47.8-72.9）。联合治疗组中位 PFS 为 10.8 个月（95%可信区间：5.6-12.7），单药治疗组为 6.5 个月（95%可信区间：5.4-8.5）[风险比（HR）0.69；95%可信区间：0.4-1.1，探索性 P 值=0.12]。探索性分析显示，联合治疗组的 PFS 优势见于接受 ET 治疗时间超过 6 个月的亚组患者（HR 0.53；95%可信区间：0.3-0.9，探索性 P 值=0.02），但在接受 ET 治疗时间≤6 个月的患者中未观察到这一优势。
结论
帕博西尼作为一种单药治疗在经过适度预处理的雌激素受体阳性、HER2 阴性晚期乳腺癌患者中具有临床活性。帕博西利可能具有逆转既往对内分泌治疗有持久反应的患者内分泌耐药的潜力。
临床试验信息
NCT02549430。
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