Deutenzalutamide, a novel androgen receptor inhibitor, after progression on docetaxel and abiraterone in metastatic castration-resistant prostate cancer: results from the randomized phase III HC-1119-04 trial

Clinical Snapshot

Key Findings

• P Value: P = 0.0001 for rPFS

• Effect Size: 42% reduction in progression risk

• Primary Outcome: Radiographic progression-free survival significantly improved with deutenzalutamide

• Nnt Or Sensitivity: Hazard ratio 0.58 for rPFS; adjusted OS HR 0.65-0.73

• Confidence Interval: Not provided in abstract

Clinical Application

Once-daily oral dosing appears feasible with manageable toxicity profile Would require TGA approval and PBS listing consideration. Fits treatment sequence after current PBS-listed therapies (abiraterone, docetaxel). RACGP guidelines would need updating to include this option Men with mCRPC who have progressed on abiraterone and docetaxel, representing a population with limited treatment options

Abstract

Metastatic castration-resistant prostate cancer (mCRPC) after treatment with docetaxel and androgen receptor signaling inhibitors (ARSIs) has limited treatment options. Although enzalutamide has shown activity after abiraterone and docetaxel, robust evidence from randomized phase III trials is lacking. Deutenzalutamide, a novel derivative with slower metabolism and improved pharmacokinetics, may offer enhanced safety and efficacy. This phase III, double-blind trial conducted at 36 centers in China enrolled patients whose disease progressed on or who were intolerant to abiraterone and docetaxel, or who were ineligible for docetaxel. Patients were randomized (2:1) to receive deutenzalutamide 80 mg once daily or placebo until progression or unacceptable toxicity; the primary endpoint was radiographic progression-free survival (rPFS). Of 417 patients (276 deutenzalutamide; 141 placebo), all had previously received abiraterone, and 68% had also received docetaxel. Deutenzalutamide significantly improved rPFS (HR, 0.58; P = 0.0001), reducing the risk of progression by 42%. Although the initial OS analysis was not significant (HR, 0.95), sensitivity analyses adjusting for subsequent therapies showed significant OS benefits (HR, 0.65-0.73). Treatment-related grade 3 or higher adverse events occurred in 22.3% of patients treated with deutenzalutamide, compared with 15.0% with placebo. The most common treatment-related adverse event was anemia, reported at any grade in 21.2% versus 17.9%, with grade 3/4 anemia in 6.6% versus 2.9%, respectively. Notably, no seizures or falls were reported. In summary, deutenzalutamide significantly prolonged rPFS and, after adjustment, showed a potential OS benefit with a favorable safety profile, supporting its promise as a new treatment option for mCRPC. Clinical trial registration: NCT03851640.

References

1. 1.Wu, J., Li, X., Gu, C., Hua, L., Liu, R., Li, J., Qiu, M., Guo, J., Dong, H., Ji, Z., Xie, L., Zhu, S., Zhang, X., Chen, P., Jiang, S., Sun, Z., Xu, D., Chen, H., Shi, B., Wang, Y., Pu, J., Perabo, F., Chen, Y., & Ye, D. (2026). Deutenzalutamide, a novel androgen receptor inhibitor, after progression on docetaxel and abiraterone in metastatic castration-resistant prostate cancer: results from the randomized phase III HC-1119-04 trial. Signal Transduction and Targeted Therapy. https://doi.org/10.1007/s40273-014-0145-y