First report of the phase I LuPARP trial assessing 177Lu-DOTATATE in combination with the PARP inhibitor olaparib in patients with somatostatin positive tumors

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Introduction: Patients with metastatic somatostatin receptor positive tumors can be treated with peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE. However, all patients do not respond sufficiently, and further treatment optimization is highly warranted. We hypothesize that the tumoricidal effect could be increased by adding a PARP inhibitor which will decrease the ability of the tumor cells to repair DNA-damage, making them more sensitive to radiation and increase the probability of tumor cell death.

Aim(s): To assess the toxicity and feasibility of the combined treatment strategy of 177Lu-DOTATATE and the PARP-inhibitor olaparib in a clinical phase I trial.

Materials and methods: Patients received 7400 MBq 177Lu-DOTA-TATE i.v. followed by 4 weeks of olaparib p.o every 8-12 weeks for 4 cycles. The olaparib dose was individually escalated from 50 to 300 mg BID if no dose-limiting toxicities (DLT) occurred. The primary objective was to assess toxicity measured by NCI Common Toxicity Criteria v 5.0.

Conference:

Presenting Author: Hallqvist A

Authors: Hallqvist A, Sjögren M, Krantz T, Holgersson K, Svensson J,

Keywords: PRRT, 177Lu-DOTATATE, olaparib,