New combination therapy safe and feasible for neuroendocrine tumor patients

Reston, VA (May 21, 2025)—A new combination therapy that pairs a radiopharmaceutical (¹⁷⁷Lu-DOTATATE) with a DNA-repair blocker (olaparib) has been deemed feasible and tolerable for neuroendocrine cancer patients. The combined therapy works by preventing cancer cells from repairing themselves after targeted treatment and has the potential to help patients achieve longer-lasting disease control. This research was published in the May issue of The Journal of Nuclear Medicine.

¹⁷⁷Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) is a mainstay strategy for low- to intermediate-grade metastatic neuroendocrine tumor patients. While this targeted radiopharmaceutical therapy provides long-term treatment effects—sometimes lasting for several years—ultimately all patients will experience disease progression.

“In preclinical trials, PARP (poly[adenosine diphosphate–ribose] polymerase) inhibition has been identified as a promising strategy for enhancing PRRT efficacy,” said Andreas Hallqvist, MD, PhD, associate professor, senior consultant, and head of the Department of Oncology at Sahlgrenska University Hospital in Gothenburg, Sweden. “Given its success, my colleagues and I sought to further explore this treatment strategy in the clinical setting.”

In the study, researchers combined ¹⁷⁷Lu-DOTATATE PRRT with olaparib, a PARP inhibitor that increases the likelihood of tumor cell death by preventing effective repair of radiation-induced damage. Eighteen patients received ¹⁷⁷Lu-DOTATATE PRRT followed by escalating doses of olaparib (50-300 mg twice a day) for up to four cycles. Toxicity was evaluated using National Cancer Institute Common Toxicity Criteria version 5.0. Time to progression, overall survival, response rate and dosimetry variables were also measured.

The combination of ¹⁷⁷Lu-DOTATATE and olaparib was generally well tolerated. Thrombocytopenia was the primary dose-limiting toxicity, observed in three patients at the 300 mg dose level. Other toxicities were mild, predominantly low-grade bone marrow suppression, nausea, and fatigue. At the six month follow-up assessment, a 69 percent disease control rate was observed.

“Our study demonstrates the potential to further improve nuclear medicine by combining targeted radiotherapy with drugs that increase the efficacy,” said Hallqvist. “This paves the way for smarter, more personalized cancer treatments. It’s our hope that more patients can receive the benefits from nuclear medicine, such as this combined therapy, in the future.”

The authors of “¹⁷⁷Lu-DOTATATE in Combination with PARP Inhibitor Olaparib Is Feasible in Patients with Somatostatin-Positive Tumors: Results from the LuPARP Phase I Trial” include Andreas Hallqvist, Elva Brynjarsdóttir, and Johanna Svensson, Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden, and Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden;Tomas Krantz and Marie Sjögren, Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden; and Peter Bernhardt, Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden, and Department of Medical Physics and Medical Bioengineering, Sahlgrenska University Hospital, Gothenburg, Sweden.

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