177Lu-DOTATATE in Combination with PARP Inhibitor Olaparib Is Feasible in Patients with Somatostatin-Positive Tumors: Results from the LuPARP Phase I Trial

This phase I trial aimed to assess the feasibility and toxicity of combining the poly(adenosine diphosphate–ribose) polymerase inhibitor olaparib with ¹⁷⁷Lu-DOTATATE in patients with somatostatin receptor–positive tumors, with the goal of enhancing treatment efficacy through the inhibition of tumor cell DNA repair mechanisms. Methods: Eighteen patients were enrolled, mostly with pancreatic or small intestinal neuroendocrine tumors or atypical lung carcinoids. Patients received a standard dose of ¹⁷⁷Lu-DOTATATE (7,400 MBq) for up to 4 cycles, combined with escalating doses of olaparib (50–300 mg twice a day [BID]). The primary objective was to evaluate toxicity using National Cancer Institute Common Toxicity Criteria version 5.0. Secondary objectives included time to progression, overall survival, response rate, and dosimetry variables. Results: The combination of olaparib and ¹⁷⁷Lu-DOTATATE was generally well tolerated. Five patients did not complete the 4 cycles because of progression, noncompliance, and carcinoid crisis after the first ¹⁷⁷Lu-DOTATATE infusion. Among the remaining patients, thrombocytopenia was the primary dose-limiting toxicity, observed in 3 patients at the 300-mg dose level. Other toxicities were mild, predominantly low-grade bone marrow suppression, nausea, and fatigue. Conclusion: This study demonstrates that combining olaparib with ¹⁷⁷Lu-DOTATATE is feasible, with toxicity primarily related to thrombocytopenia. On the basis of the findings, we recommend a starting dose of 200 mg BID for future studies, with the potential to escalate to 300 mg BID depending on patient tolerance. Further investigation in larger, randomized trials is warranted to assess the clinical efficacy of this combination and optimize dosing strategies.