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Updated: Jun 17, 2026
07:25
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
13.3K
Orteronel for Metastatic Hormone-Sensitive Prostate Cancer: A Multicenter, Randomized, Open-Label Phase III Trial
Neeraj Agarwal1, Catherine M Tangen2, Maha H A Hussain3
1University of Utah Huntsman Cancer Institute, Salt Lake City, UT.
Summary
Orteronel did not improve overall survival in metastatic hormone-sensitive prostate cancer patients when added to androgen deprivation therapy (ADT). While progression-free survival and PSA response improved, overall survival was not significantly impacted.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Prostate cancer is a leading cause of cancer death in men.
- Androgen deprivation therapy (ADT) is a standard treatment for metastatic hormone-sensitive prostate cancer (mHSPC).
- Orteronel is a nonsteroidal 17,20-lyase inhibitor designed to suppress androgen synthesis.
Purpose of the Study:
- To evaluate the clinical benefit of adding orteronel to ADT in patients with newly diagnosed mHSPC.
- To compare overall survival (OS) between patients receiving ADT plus orteronel versus ADT plus bicalutamide.
Main Methods:
- An open-label, randomized phase III study involving 1,279 mHSPC patients.
- Patients were assigned 1:1 to receive ADT with orteronel or ADT with bicalutamide.
- Primary endpoint was OS; secondary endpoints included progression-free survival (PFS) and prostate-specific antigen (PSA) response.
Main Results:
- Orteronel did not significantly improve median overall survival (81.1 vs. 70.2 months; P=0.040, one-sided).
- Progression-free survival (PFS) was significantly improved with orteronel (median 47.6 vs. 23.0 months; P < .0001).
- Higher rates of grade 3/4 adverse events were observed in the orteronel arm (43% vs. 14%).
Conclusions:
- The study did not meet its primary endpoint of improved overall survival with orteronel plus ADT.
- The findings raise concerns about the reliability of PFS and PSA response as surrogates for OS in mHSPC, especially with extensive post-protocol therapy.
- Orteronel was associated with a higher incidence of severe adverse events compared to bicalutamide.
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