Palbociclib and Trastuzumab in HER2-Positive Advanced Breast Cancer: Results from the Phase II SOLTI-1303 PATRICIA Trial
Palbociclib and Trastuzumab in HER2-Positive Advanced Breast Cancer: Results from the Phase II SOLTI-1303 PATRICIA Trial
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DOI：
10.1158/1078-0432.ccr-20-0844
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发表时间：
2020-11-15
影响因子：
11.5
通讯作者：
Prat, Aleix
中科院分区：
文献类型：
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作者：
Ciruelos, Eva;Villagrasa, Patricia;Prat, Aleix
目的：评估Palbociclib联合曲妥珠单抗联合或不联合内分泌治疗在HER 2阳性晚期乳腺癌患者中的疗效。患者和方法：PATRICIA是一项前瞻性、开放标签、多中心II期试验。患者既往接受过2-4线基于抗HER 2的治疗方案。治疗包括palbociclib 200 mg每日一次，持续2周，停药1周+曲妥珠单抗。该研究基于Simon两阶段设计，包括三个队列：雌激素受体（ER）阴性（队列A）、ER阳性（队列B1）和ER阳性（队列B2）。ER阳性患者随机分配至队列B1或B2。主要终点是6个月时的无进展生存率（PFS 6）。次要目的包括安全性和评价的PAM 50内在subtypes.Results：71例患者被招募（n = 15在队列A和28在每个队列B）。队列A、B1和B2的PFS 6率分别为33.3%（5/15）、42.8%（12/28）和46.4%（13/28）。关于安全性，97.7%和84.4%的患者分别发生了1-2级和3-4级毒性。最常见的3-4级毒性为中性粒细胞减少（66.4%）和血小板减少（11.3%）。关于PAM 50，对59例（83.1%）肿瘤进行了分析。与非管腔性疾病相比，发现由PAM 50定义的管腔性疾病与PFS延长独立相关（10.6个月vs. 4.2个月的中位PFS;调整后的风险比= 0.40; P = 0.003）。Palbociclib与曲妥珠单抗联合治疗在曲妥珠单抗预处理的ER阳性/HER 2-PAM 50 Luminal A或B亚型阳性晚期乳腺癌。提前停止入组，并在该人群中开放了一个新的随机队列。
Purpose: To assess palbociclib in combination with trastuzumab with or without endocrine therapy in patients with HER2-positive advanced breast cancer.Patients and Methods: PATRICIA is a prospective, open-label, multicenter phase II trial. Patients had received 2-4 prior lines of anti-HER2-based regimens. Treatment consisted of palbociclib 200 mg daily for 2 weeks and 1 week off plus trastuzumab. The study was based on a Simon two-stage design comprising three cohorts: estrogen receptor (ER)-negative (cohort A), ER-positive (cohort B1), and ER-positive with letrozole (cohort B2). ER-positive patients were randomized to cohorts B1 or B2. Primary endpoint was progression-free survival rate at 6 months (PFS6). Secondary objectives included safety and evaluation of the PAM50 intrinsic subtypes.Results: Seventy-one patients were recruited (n = 15 in cohort A and 28 in each cohort B). The PFS6 rate in cohorts A, B1, and B2 was 33.3% (5/15), 42.8% (12/28), and 46.4% (13/28), respectively. Regarding safety, grade 1-2 and 3-4 toxicities occurred in 97.7% and 84.4% of patients, respectively. The most common grade 3-4 toxicities were neutropenia (66.4%) and thrombocytopenia ( 11.3%). Regarding PAM50, 59 (83.1%) tumors were profiled. Luminal disease defined by PAM50 was found independently associated with longer PFS compared with non-luminal disease (10.6 vs. 4.2 months median PFS; adjusted hazard ratio = 0.40; P = 0.003).Conclusions: Palbociclib in combination with trastuzumab is safe and exhibits promising survival outcomes in trastuzumab pretreated ER-positive/HER2-positive advanced breast cancer with a PAM50 Luminal A or B subtype. The enrollment was stopped prematurely, and a new randomized cohort was opened in this population.