Successful Combination of Olaparib and ²²⁵Ac-Dotatate in a Patient with Neuroendocrine Tumor G3 and BRCA Mutation

Based on the results of the NETTER-1 trial, peptide receptor radionuclide therapy with Lutetium-177 (¹⁷⁷Lu) - DOTATATE is authorized for the treatment of neuroendocrine tumors (NET) grade 1 (G1) and grade 2 (G2) of the intestine. After the failure of ¹⁷⁷Lu-DOTATATE therapy, targeted alpha-particle therapy (TAT) may be a possible treatment option. Here, we present a patient with cancer of unknown primary 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 revealed a huge pelvic tumor without metastases. 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 months indicating that a combination therapy with an alpha emitter and olaparib demands further investigations in clinical trials.