orteronel (TAK 700)

P3, N=239, Completed, Radiation Therapy Oncology Group | Active, not recruiting --> Completed | Trial completion date: Jun 2029 --> Sep 2025

The demonstrated delays in definitive deterioration in GHS/QoL, urinary symptoms, and other functioning and symptom scales with talazoparib plus enzalutamide compared with placebo plus enzalutamide in patients with HRR-deficient metastatic castration-resistant prostate cancer provide insight that might inform clinical decisions for these patients.

Low accrual led to an early interruption of the study. However, orteronel achieved a promising clinical benefit rate that supports further development of new hormonotherapies in this tumor.

In this planned S1216 subset analysis of men with HSPC and bone metastases, elevated serum markers of bone metabolism were significantly associated with worse OS. Bone biomarker levels alone and in combination with patient and tumor characteristics identify unique subsets of men with differential OS outcomes.

P3, N=1313, Active, not recruiting, SWOG Cancer Research Network

Concerning OS, ADT + abiraterone, ADT + abiraterone + docetaxel, ADT + apalutamide, ADT + bicalutamide, ADT + darolutamide + docetaxel, ADT + enzalutamide, ADT + orteronel, and ADT + rezvilutamide were more effective than the standard of care (SOC). Comparing PFS, most treatments were more effective than SOC, excluding ADT + bicalutamide, nilutamide, flutamide, ADT + bicalutamide + palbociclib, and ADT + nilutamide...Novel oral chemotherapeutic agent combination therapies must replace current ADT monotherapy and ADT + docetaxel SOC. Even so, ADT + docetaxel with ARTA triplet therapy still is not the best mHSPC treatment and requires further study.

Patients receiving androgen deprivation therapy were randomized (1:1) to receive either orteronel 300 mg orally twice daily (experimental group) or bicalutamide 50 mg orally daily (control group). Equitable access to care may reduce historical differences in outcomes between Black and White patients with advanced prostate cancer. ClinicalTrials.gov Identifier: NCT01809691.

In men with HSPC initiating androgen deprivation therapy, bone biomarkers are strongly and independently prognostic for OS. Bone biomarker levels alone or in combination with clinical covariates identify unique subsets of men with differential OS outcomes. These results validate the clinical value of bone biomarker assessment in the HSPC state, extending bone biomarker utility beyond the castration-resistant state.

CTC count at the start of treatment for mHSPC was highly prognostic of PSA response, PFS, and OS; associations that held in both treatment arms. Moreover, baseline CTC count strongly correlated with progression count, suggesting that mild vs. aggressive disease phenotypes may persist from mHSPC to mCRPC.

MD simulation study reveals stable binding of Friedelin to conserved binding pocket of CYP17A1 with higher binding affinity than studied control, that is, Orteronel...Thus, we propose Friedelin and CT extract as potential leads, which could be taken further for drug development in PC. Communicated by Ramaswamy H. Sarma.