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AACR 2023: Darolutamide-Based Combination Therapy for Metastatic Castration-Resistant Prostate Cancer

By: Joshua D. Madera, MS
Posted: Thursday, May 4, 2023

For patients with metastatic castration-resistant prostate cancer, the use of combination therapy with ONC201 and the next-generation androgen receptor signaling inhibitor darolutamide may lead to improved therapeutic outcomes, according to a preclinical presentation given at the American Association for Cancer Research (AACR) Annual Meeting 2023 (Abstract 1672/29). These findings suggest that additional investigative efforts are warranted to establish more efficient anticancer strategies, suggested Maximilian Schwermann, MD, of Brown University, Providence, Rhode Island, and colleagues.

A subcutaneous metastatic castration-resistant prostate cancer mouse xenograft model was developed to determine the efficacy of combination treatment in vivo. A digital caliper and bioluminescent imaging were consistently employed to monitor tumor growth. When the tumors reached 150 mm3, mice were randomly stratified to receive either 50 mg/kg of darolutamide, 20 mg/kg of enzalutamide, 50 mg/kg or 100 mg/kg of ONC201, or a combination of these treatments. All mice received their respective treatments for 36 days.

The study findings revealed that mice receiving 100 mg/kg of ONC201 alone showed the highest level of antitumor efficacy. In mice receiving 100 mg/kg of ONC201 in combination with another type of therapy, partial tumor regression was observed. In addition, on flow cytometry, mice treated with any dose of ONC201 showed higher levels of intratumor natural killer (NK) cells. This same trend was observed in mice receiving ONC201 in combination with darolutamide. Moreover, evidence of elevated tumor necrosis factor–related apoptosis-inducing ligand activation within NK cells was observed across all treatment groups.

Disclosure: The study authors reported no conflicts of interest.

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