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ASCO 2023: Early-Phase Trial of Radionuclide Therapy Plus Olaparib in Metastatic Prostate Cancer

By: Celeste L. Dixon
Posted: Monday, June 5, 2023

Results of a phase I study indicate that the combination of lutetium-177–labeled PSMA-617 (LuPSMA) and olaparib—a prostate-specific membrane antigen (PSMA)-directed, radionuclide therapy and a PARP inhibitor, respectively—is well tolerated and has measurable activity against metastatic castration-resistant prostate cancer. Shahneen Sandhu, MD, of Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia, and colleagues presented the results of the LuPARP study at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 5005). The primary objectives were to establish any dose-limiting toxicities and the recommended phase II dose.

So far, 29 patients with metastatic castration-resistant prostate cancer and high PSMA expression have been treated. Each received LuPSMA on day 1 of each cycle and then continued with one of nine prespecified olaparib dosing schedules for up to six cycles. A total of 18 responded with at least a 50% decline in prostate-specific antigen from baseline, and five of the seven patients with measurable disease (as defined by Response Evaluation Criteria in Solid Tumors) had a partial response to the regimen. No dose-limiting toxicities were reported, although most patients experienced treatment-related adverse events ranging from xerostomia (83%) to transient grade 3 neutropenia (7%).

To date, “although many patients benefit from treatment [with LuPSMA alone], approximately a third have primary resistance, median progression-free survival is 5.1 months, and all patients inevitably relapse,” Dr. Sandhu and co-investigators pointed out. Three additional patients will be enrolled to cohort 9 to confirm the recommended phase II dose ahead of dose expansion. The researchers project that 48 patients will ultimately participate in LuPARP.

Disclosure: The study authors’ disclosure information can be found at

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