Department of Nuclear Medicine and Endocrine Oncology, Gliwice Branch, Maria Sklodowska-Curie National Research Institute of Oncology, Wybrzeże Armii Krajowej 16, 44-101, Gliwice, Poland.
The Oncologic and Reconstructive Surgery Clinic, Gliwice Branch, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice, Poland.
Eur J Nucl Med Mol Imaging. 2022 Sep;49(11):3841-3851. doi: 10.1007/s00259-022-05792-y. Epub 2022 May 3.
Peptide receptor radionuclide therapy (PRRT) and somatostatin analogues (SSAs) are commonly combined as primary treatment for neuroendocrine neoplasms (NEN), and SSAs given as maintenance. We sought to evaluate whether sequential therapy with PRRT followed by SSAs has progression or survival benefits in patients with NEN after disease control by PRRT.
This prospective, randomised, single-centre study had as principal eligibility criteria: unresectable, locally advanced, or metastatic, histologically confirmed well-differentiated NEN; no symptoms/biochemical diagnosis of carcinoid syndrome; no SSAs or ≤ 3 months of SSAs before PRRT; and stable disease or partial or complete response after PRRT. Altogether, 115 patients were randomised 2:1 to an SSA group (n = 74) given octreotide acetate LAR every 4 weeks, or a control group (n = 41) receiving only best supportive care. Octreotide treatment was to stop upon intolerable toxicity or patient refusal, or, at physician/patient discretion, upon NEN progression. The primary endpoint was progression-free survival (PFS), the secondary endpoint, and overall survival (OS).
Median (25th-75th percentile) follow-up from the first PRRT activity to death or latest observation was 6.6 (3.18-10.22) years. During that time, 71/115 patients (62%) progressed, 52/74 (70%) in the SSA group, and 19/41 (46%) in the control group (p = 0.01). Eighty-eight/115 patients (76%) died, 58/74 (78%) in the SSA group, and 30/41 (73%) in the control group (p = 0.52). Median (95% CI) PFS was 4.7 (2.8-7.7) years in the SSA group, and 6.4 (4.1-not reached) years in controls. Overall, median OS was 6.6 years. Neither PFS nor OS differed between groups (p = 0.129, p = 0.985, respectively).
In patients with disease control after PRRT, subsequent SSA treatment appeared not to be associated with better PFS or OS. Whether to continue SSA administration upon progression after PRRT requires evaluation in a prospective, randomised, controlled multicentre study with a relatively homogeneous sample.
肽受体放射性核素疗法（PRRT）和生长抑素类似物（SSAs）通常联合作为神经内分泌肿瘤（NEN）的初始治疗方法，并作为维持治疗。我们旨在评估在 PRRT 控制疾病后，对于 NEN 患者，PRRT 后序贯 SSAs 治疗是否具有进展或生存获益。
这是一项前瞻性、随机、单中心研究，其主要纳入标准为：无法切除的、局部晚期或转移性、组织学证实的分化良好的 NEN；无类癌综合征的症状/生化诊断；在 PRRT 前无 SSAs 或≤3 个月的 SSAs 治疗史；PRRT 后疾病稳定或部分或完全缓解。共 115 例患者按 2:1 的比例随机分为 SSA 组（n=74），给予醋酸奥曲肽 LAR 每 4 周一次；或对照组（n=41），仅接受最佳支持治疗。奥曲肽治疗应在不可耐受的毒性或患者拒绝或根据医生/患者的决定，在 NEN 进展时停止。主要终点为无进展生存期（PFS），次要终点为总生存期（OS）。
从第一次 PRRT 活性到死亡或最后观察的中位（25 至 75 百分位数）随访时间为 6.6（3.18-10.22）年。在此期间，115 例患者中有 71 例（62%）进展，SSA 组 52 例（70%），对照组 19 例（46%）（p=0.01）。115 例患者中有 88 例（76%）死亡，SSA 组 58 例（78%），对照组 30 例（73%）（p=0.52）。SSA 组的中位（95%CI）PFS 为 4.7（2.8-7.7）年，对照组为 6.4（4.1-未达到）年。总体而言，中位 OS 为 6.6 年。两组间 PFS 或 OS 均无差异（p=0.129，p=0.985）。
在 PRRT 后疾病得到控制的患者中，随后的 SSA 治疗似乎并不能带来更好的 PFS 或 OS。在 PRRT 后疾病进展时是否继续给予 SSA 治疗，需要在一项具有相对同质样本的前瞻性、随机、对照、多中心研究中进行评估。
