Department of Medical Oncology, MD Anderson Cancer Center Madrid, Madrid, Spain.
Department of Medical Oncology, Catalan Institute of Oncology (Hospital Duran i Reynals), L'Hospitalet, Barcelona, Spain.
Oncologist. 2020 Sep;25(9):745-e1265. doi: 10.1634/theoncologist.2020-0033. Epub 2020 Feb 11.
Palbociclib demonstrated no detectable activity in molecularly unselected and heavily pretreated patients with advanced grade 1/2 pancreatic neuroendocrine tumors. Predictive biomarkers that improve patient selection should be investigated in future studies of palbociclib.
Palbociclib, a CDK4/6 inhibitor, has shown in vitro activity in pancreatic neuroendocrine tumor (pNET) cell lines. Here we prospectively assessed the activity and safety of palbociclib in monotherapy in metastatic refractory pNETs.
This was a nonrandomized, open-label, phase II study of patients with metastatic grade (G)1/2 pNETs recruited from 10 centers in Spain. Palbociclib 125 mg was orally administered once daily for 21 of 28 days until disease progression or unacceptable toxicity.
Twenty-one patients were included; 52.4% were men, and median age was 57.4 years (range, 37.4-73.4). Patients had previously received a median of three prior lines of systemic therapy (range, 1-10) for advanced disease (somatostatin analogues, 71.4%; sunitinib, 81.0%; everolimus, 47.6%; chemotherapy, 47.6%). Nineteen patients were evaluated for objective response rate (ORR), with a median follow-up of 12.4 months (range, 7.53-19.33). No objective and confirmed responses were observed (0%); 11 (57.9%) patients had stable disease, and 6 of them lasted more than 6 months; 8 (42.1%) patients had disease progression as best response. Median progression-free survival (PFS) was 2.6 months (95% confidence interval [CI], 0-14.4) and median overall survival (OS) was 18.7 months (95% CI, 7.4-29.9; Fig. 1). Most frequent toxicities of any grade were asthenia (76.2%), neutropenia (42.9%), diarrhea (33.3%), and nausea (33.3%). Five (23.8%) patients developed G3-4 neutropenia and two (9.5%) patients developed G3-4 thrombocytopenia.
Lack of activity was observed with palbociclib as a single agent in molecularly unselected and heavily pretreated patients with advanced G1/2 pNETs.
帕博西尼在未进行分子选择且经过大量预处理的晚期 1/2 级胰腺神经内分泌肿瘤患者中未显示出可检测到的活性。应在未来的帕博西尼研究中探索能够改善患者选择的预测性生物标志物。
帕博西尼（一种 CDK4/6 抑制剂）在胰腺神经内分泌肿瘤（pNET）细胞系中表现出体外活性。在此，我们前瞻性评估了帕博西尼单药治疗转移性难治性 pNET 的活性和安全性。
这是一项在西班牙 10 个中心招募的转移性 1/2 级 G pNET 患者进行的非随机、开放标签、II 期研究。帕博西尼 125 mg 每日口服一次，28 天疗程中连用 21 天，直至疾病进展或出现无法耐受的毒性。
共纳入 21 例患者；52.4%为男性，中位年龄为 57.4 岁（范围为 37.4-73.4）。患者既往接受过中位三线治疗（范围为 1-10 线）用于晚期疾病（生长抑素类似物，71.4%；舒尼替尼，81.0%；依维莫司，47.6%；化疗，47.6%）。19 例患者可评估客观缓解率（ORR），中位随访时间为 12.4 个月（范围为 7.53-19.33）。未观察到客观和确认的缓解（0%）；11 例（57.9%）患者疾病稳定，其中 6 例持续时间超过 6 个月；8 例（42.1%）患者疾病进展为最佳缓解。中位无进展生存期（PFS）为 2.6 个月（95%置信区间 [CI]，0-14.4），中位总生存期（OS）为 18.7 个月（95%CI，7.4-29.9；图 1）。任何级别最常见的毒性是乏力（76.2%）、中性粒细胞减少（42.9%）、腹泻（33.3%）和恶心（33.3%）。5 例（23.8%）患者发生 3/4 级中性粒细胞减少，2 例（9.5%）患者发生 3/4 级血小板减少。
在未进行分子选择且经过大量预处理的晚期 G1/2 级 pNET 患者中，帕博西尼单药治疗未显示出活性。
