Nasca Vincenzo, Prinzi Natalie, Coppa Jorgelina, Prisciandaro Michele, Oldani Simone, Ghelardi Filippo, Conca Elena, Capone Iolanda, Busico Adele, Perrone Federica, Tamborini Elena, Sabella Giovanna, Greco Giorgio, Greco Francesca Gabriella, Tafuto Salvatore, Procopio Giuseppe, Morano Federica, Niger Monica, Maccauro Marco, Milione Massimo, de Braud Filippo, Pietrantonio Filippo, Pusceddu Sara
Department of Medical Oncology, Fondazione IRCCS Istituto Tumori Milano, Milan, Italy.
Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Eur J Cancer. 2024 Sep;209:114276. doi: 10.1016/j.ejca.2024.114276. Epub 2024 Aug 9.
Metastatic Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors characterized by high morbidity and limited systemic treatment options, mainly based on radiometabolic treatments or chemotherapy. Based on the preclinical rationale that PGGLs carcinogenesis relies on angiogenesis, treatment with tyrosine kinase inhibitors (TKI) may represent another viable therapeutic option.
We conducted a prospective phase II study in patients with metastatic or unresectable PGGLs. Patients received sunitinib (50 mg daily for 4 weeks, followed by a 2-week rest period) until progressive disease (PD), unacceptable toxicity or consent withdrawal. The primary endpoint was 12-month progression-free survival (PFS) rate; secondary endpoints were safety overall response rate (ORR) according to RECIST 1.1 criteria and overall survival (OS). EudraCT Number: 2011-002632-99.
Fifty patients were included. At a median follow-up of 71.7 months (IQR 35.4-100.1), the 1 year-PFS rate was 53.4 % (95 %CI 41.1-69.3) and median PFS was 14.1 months (95 % CI 8.9-25.7). ORR was 15.6 %, the median OS was 49.4 months (95 %CI 21.2-NA), and grade 3 or higher treatment-related adverse events were reported in 34 % patients. No significant correlation was found between specific genetic alterations or genomic clusters and sunitinib efficacy.
Sunitinib is an active drug in patients with advanced PGGLs, capable of inducing prolonged disease control with a manageable toxicity profile.
转移性嗜铬细胞瘤和副神经节瘤（PPGLs）是罕见的神经内分泌肿瘤，其特征为发病率高且全身治疗选择有限，主要基于放射性代谢治疗或化疗。基于PPGLs致癌作用依赖血管生成的临床前理论依据，酪氨酸激酶抑制剂（TKI）治疗可能是另一种可行的治疗选择。
我们对转移性或不可切除的PPGLs患者进行了一项前瞻性II期研究。患者接受舒尼替尼（每日50mg，共4周，随后休息2周），直至疾病进展（PD）、出现不可接受的毒性或患者撤回同意。主要终点是12个月无进展生存期（PFS）率；次要终点是安全性、根据RECIST 1.1标准的总缓解率（ORR）和总生存期（OS）。欧洲临床试验注册号：2011-002632-99。
纳入了50例患者。中位随访71.7个月（四分位间距35.4 - 100.1），1年PFS率为53.4%（95%CI 41.1 - 69.3），中位PFS为14.1个月（95%CI 8.9 - 25.7）。ORR为15.6%，中位OS为49.4个月（95%CI 21.2 - 无可用数据），34%的患者报告了3级或更高等级的治疗相关不良事件。未发现特定基因改变或基因组簇与舒尼替尼疗效之间存在显著相关性。
舒尼替尼是晚期PPGLs患者的一种有效药物，能够诱导疾病得到长期控制，且毒性可控。
