Related Experiment Video
Updated: Oct 12, 2025
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
A Phase II Study Evaluating Orteronel, an Inhibitor of Androgen Biosynthesis, in Patients With Androgen Receptor
Denise A Yardley1, Robyn R Young2, Kerin B Adelson3
1Sarah Cannon Research Institute, Nashville, TN; Tennessee Oncology, PLLC, Nashville, TN.
Background:
AR is a targetable pathway with AR modulation inhibiting estrogen- and androgen-mediated cell proliferation. Orteronel is an oral, selective, nonsteroidal inhibitor of 17, 20-lyase, a key enzyme in androgen biosynthesis. This study evaluated single-agent orteronel in AR+ metastatic breast cancer (MBC).
Methods:
Male/female patients with AR+ MBC were grouped in Cohort 1: AR+ TNBC with l-3 prior chemotherapy regimens or Cohort 2: AR+ HR+ (estrogen [ER+]/ progesterone receptor [PR+] positive) HER2+/- with 1 to 3 prior hormonal and at least 1 prior chemotherapy regimen. Patients with HER2+ MBC must have received at least 2 lines of HER2-targeted therapy. Orteronel was administered at 300 mg BID; response rate was the primary endpoint.
Results:
Seventy patients were enrolled (Cohort 1, n = 26 and Cohort 2, n = 44). Median treatment duration was 7.1 weeks. Seven patients were on treatment for ≥6 months. One of the 21 evaluated patients in Cohort 1 (4.8%) had an objective response. In Cohort 2, none of the first 23 patients to be evaluated had a response and accrual was stopped. Median progression-free and overall survival were 1.8 and 8.3 months, respectively. Toxicities were predominantly Grade 1 or 2 nausea/vomiting (36%) and fatigue (31%). Grade 3 or 4 events in ≥5% of patients included increased amylase/lipase (10%) and hypertension (6%).
Conclusions:
Orteronel demonstrated limited clinical activity in heavily pre-treated AR+ MBC. Further development of orteronel in MBC is not recommended. Further efforts to validate the AR as a therapeutic target should focus on identifying new markers predictive of sensitivity to AR-targeted agents.
Insights
Orteronel showed limited effectiveness in heavily pre-treated androgen receptor-positive metastatic breast cancer (AR+ MBC). Further development of orteronel for AR+ MBC is not recommended due to minimal clinical activity.
Area of Science:
- Oncology
- Pharmacology
- Genetics
Background:
- Androgen receptor (AR) is a targetable pathway in cancer.
- Orteronel inhibits androgen biosynthesis by targeting 17, 20-lyase.
- AR modulation can inhibit cancer cell proliferation.
Purpose of the Study:
- To evaluate the efficacy of single-agent orteronel in AR-positive metastatic breast cancer (AR+ MBC).
- To assess response rates and safety of orteronel in heavily pre-treated patients.
Main Methods:
- Two cohorts of AR+ MBC patients were enrolled: TNBC (Cohort 1) and HR+ HER2+/- (Cohort 2).
- Orteronel was administered orally at 300 mg twice daily.
- Objective response rate was the primary endpoint.
Main Results:
- Seven of seventy patients (26 in Cohort 1, 44 in Cohort 2) were enrolled.
- Objective response was observed in 1 of 21 evaluated patients in Cohort 1 (4.8%).
- No responses were observed in Cohort 2, leading to study discontinuation; toxicities included nausea, vomiting, fatigue, and elevated amylase/lipase.
Conclusions:
- Orteronel demonstrated limited clinical activity in heavily pre-treated AR+ MBC.
- Further development of orteronel in this patient population is not recommended.
- Future research should identify biomarkers for AR-targeted therapy sensitivity.
