Supplementary Material for: Successful Combination of Olaparib and 225Ac-Dotatate in a Patient with NET G3 and BRCA mutation

Based on the results of the NETTER-1 trial, peptide receptor radionuclide therapy (PRRT) with Lutetium-177 (177Lu) –DOTATATE is authorized for the treatment of neuroendocrine tumors (NET) grade 1 (G1) and G2 of the intestine. After the failure of 177Lu‑DOTATATE, targeted alpha‑particle therapy (TAT) may be a possible treatment option. Here, we present a patient with cancer of unknown primary (CUP) NET G2 later G3. The patient was referred to our hospital with urosepsis due to a second-degree urinary retention. After stent insertion, a contrast-enhanced computed tomography (CT) revealed a huge pelvic tumor without metastasis. Initially the patient had undergone surgical treatment. Later the patient developed liver metastasis and was treated by 177Lu‑DOTATATE therapy and four lines of systemic therapy. A disease progression was observed and with the knowledge of a germline BRCA1 mutation, the patient was treated with TAT (Actinium-225 (225Ac)-DOTATATE) combined with olaparib. The patient achieved a significant treatment response for 12 month indicating that a combination therapy with an alpha emitter plus olaparib might deserve further investigations in clinical trials.

本研究基于NETTER-1试验的结果，镥-177（¹⁷⁷Lu）-DOTATATE的肽受体放射性核素治疗（peptide receptor radionuclide therapy, PRRT）已获批用于治疗肠道来源的1级（G1）和2级（G2）神经内分泌瘤（neuroendocrine tumors, NET）。在¹⁷⁷Lu-DOTATATE治疗失败后，靶向α粒子治疗（targeted alpha-particle therapy, TAT）或可作为潜在治疗选择。本文报告1例原发灶不明癌（cancer of unknown primary, CUP）患者，其病理类型为NET G2，后续进展为G3。患者因二度尿潴留引发尿脓毒症就诊于我院。行支架置入术后，增强计算机断层扫描（contrast-enhanced computed tomography, CT）提示存在巨大盆腔肿瘤，未发现远处转移。患者最初接受手术治疗，后续出现肝转移，先后接受¹⁷⁷Lu-DOTATATE治疗及4线全身治疗。后观察到疾病进展，结合患者存在种系BRCA1突变（germline BRCA1 mutation），予TAT（锕-225（²²⁵Ac）-DOTATATE）联合奥拉帕利（olaparib）治疗。患者获得了长达12个月的显著治疗应答，提示α放射源联合奥拉帕利的联合治疗方案值得在临床试验中进一步探索。