orteronel (TAK 700) / Takeda - LARVOL DELTA

Cardiovascular toxicity with androgen-receptor pathway inhibitors in metastatic prostate cancer: A meta-analysis of randomized trials. (ASCO-GU 2026) - " MEDLINE, and EMBASE were systematically searched from database inception through August 30, 2025, for phase III randomized controlled trials evaluating abiraterone, enzalutamide, apalutamide, darolutamide, orteronel in metastatic prostate cancer. Current evidence indicates potentially increased risk of hypertension, venous thromboembolic, and ischemic cardiac events with ARPI therapy in metastatic prostate cancer. Proactive CV risk assessment, particularly in patients with preexisting comorbidities or prolonged ARPI exposure, may optimize outcomes and minimize treatment interruptions. All cause adverse events."

Metastases • Retrospective data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Efficacy of talazoparib and enzalutamide in mCRPC patients previously treated with androgen receptor pathway inhibitors (ARPI) or docetaxel: Post hoc analysis from both cohorts in TALAPRO-2 study (ESMO 2024) - P3 | "We conducted a post hoc analysis of radiographic progression free survival (rPFS) by prior androgen receptor pathway inhibitors (ARPI; abiraterone or orteronel) or by prior docetaxel. Time-to-event was summarized using the Kaplan-Meier method and compared between treatment arms using a stratified log-rank test except for the subgroup analysis of rPFS by prior ARPI/docetaxel which used an unstratified model due to small patient numbers in some of the subgroups. Although numbers in ARPI or docetaxel pretreated cohorts are small, this post hoc subgroup analysis shows the same improved trend in rPFS benefit by TALA+ENZA in both cohorts of the TALAPRO-2 study."

Clinical • Retrospective data • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer

First-line talazoparib plus enzalutamide versus placebo plus enzalutamide in men with metastatic castration-resistant prostate cancer and homologous recombination repair gene alterations: patient-reported outcomes from the randomised, double-blind, placebo-controlled, phase 3 TALAPRO-2 trial. (PubMed, Lancet Oncol) - P3 | "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."

Clinical • Journal • P3 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Pain • Prostate Cancer • Solid Tumor • HRD

Time to metastasis after prostatectomy (TTM) and survival outcomes in patients (pts) with metachronous metastatic hormone-sensitive prostate cancer (mHSPC): A secondary analysis of the SWOG 1216 phase 3 trial. (ASCO-GU 2025) - P3 | "Therefore, we assessed the prognostic value of TTM using the SWOG 1216 trial data which randomized pts with mHSPC to androgen deprivation therapy (ADT) with orteronel (ORT) or bicalutamide (bic) (NCT01809691). The timing of metastatic disease after prostatectomy in pts with metachronous mHSPC did not appear to be related to survival and should not be used as a prognostic factor nor to predict treatment outcomes."

Clinical • Metastases • P3 data • Castration-Sensitive Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Orteronel for Metastatic Hormone-Sensitive Prostate Cancer: A Multicenter, Randomized, Open-Label Phase III Trial (SWOG-1216). (PubMed, J Clin Oncol) - "The study did not meet the primary end point of improved OS with orteronel. The lack of correlation of PFS and PSA response with OS raises concerns over assumption of their consistent surrogacy for OS in the context of extensive postprotocol therapy in this setting."

Journal • P3 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Bone biomarkers and overall survival (OS) in men with advanced hormone-sensitive prostate cancer (HSPC): Results from SWOG S1216, a phase III trial of ADT +/- orteronel. (ASCO 2022) - P3 | "In men initiating ADT for HSPC, elevated BB are strongly prognostic for worse OS. BB levels alone & in combination with pt/tumor characteristics identify unique subsets of men with high probability of being alive at 3 years from ADT initiation. These results validate the clinical value of BB in the HSPC state, extending BB utility beyond CRPC."

Biomarker • Clinical • P3 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Prostate-specific antigen value at 3 & 7 months (PSA-3mo, PSA-7mo) and overall survival (OS) in metastatic hormone-sensitive prostate cancer (mHSPC) treated with androgen deprivation (ADT) with or without orteronel (SWOG S1216). (ASCO 2023) - P3 | "Background: Analysis of phase 3 studies of patients (pts) with mHSPC in the era of ADT, including in combination with docetaxel and/or androgen receptor axis targeted therapies have established PSA-7mo as a key prognostic marker. Our objective was to evaluate the association between PSA-3mo, PSA 7-mo and OS measured in the phase 3 S1216 trial in mHSPC comparing ADT + orteronel (treatment arm) vs ADT + bicalutamide (control arm) [NCT01809691]... PSA-3mo and PSA-7mo are strong prognostic markers for pts with mHSPC. More pts on ADT with orteronel achieved CR at 3 and 7 mo. In addition to its use in counseling patients in the clinic, PSA-3mo and PSA-7mo may be used as parameters for designing future trials in pts with mHSPC, utilizing the next generation of intensification or de-intensification treatment regimens."

Clinical • Metastases • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Outcomes of Black (B) versus White (W) patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC) treated with androgen deprivation therapy (ADT) with or without orteronel (Ort): Analysis of pt-level data from SWOG-1216 phase 3 trial. (ASCO 2023) - "In the phase 3 S1216 trial, treatment with Ort, a novel CYP17 axis inhibitor, significantly improved progression-free survival (PFS) but not overall survival (OS) compared to bicalutamide (Bic) in pts with mHSPC receiving ADT. We demonstrate that even though B pts present with more aggressive disease in mHSPC setting, they did not have statistically significant worse OS and PFS than W pts and treatment effect was also similar for both racial groups. Equitable access to care may negate historical differences in outcomes among B vs W pts with advanced PCa. Funding: NIH/NCI/NCTN grant U10CA180888, U10CA180819; and Millennium Pharmaceuticals (Takeda Oncology)."

Clinical • Metastases • P3 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Orteronel for Metastatic Hormone-Sensitive Prostate Cancer: A Multicenter, Randomized, Open-Label Phase III Trial (SWOG-1216). (SWOG-Fall 2022) - P3 | " In this open-label randomized phase III study, patients with metastatic hormone-sensitive prostate cancer were randomly assigned 1:1 to ADT with orteronel (300 mg oral twice daily; experimental arm) or ADT with bicalutamide (50 mg oral once daily; control arm). The study did not meet the primary end point of improved OS with orteronel. The lack of correlation of PFS and PSA response with OS raises concerns over assumption of their consistent surrogacy for OS in the context of extensive postprotocol therapy in this setting."

Clinical • P3 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Race and Treatment Outcomes in Patients With Metastatic Castration-Sensitive Prostate Cancer: A Secondary Analysis of the SWOG 1216 Phase 3 Trial. (PubMed, JAMA Netw Open) - P3 | "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."

Clinical • Journal • Metastases • P3 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Baseline bone pain as a prognostic marker for survival for men with metastatic hormone-sensitive prostate cancer (mHSPC): Patient-level analysis of SWOG 1216 trial. (ASCO-GU 2024) - P3 | "Therefore, SWOG 1216 trial data which randomized men with mHSPC to androgen deprivation therapy (ADT) with orteronel vs bicalutamide was evaluated (PMID: 35446628,NCT01809691). Men with mHSPC with bone pain at baseline have worse survival outcomes despite treatment intensification and may be prioritized for enrollment in clinical trials. These data may aid patient counseling and warrant the inclusion of bone pain in the prognostic models of mHSPC. Clinical trial information: NCT01809691."

Biomarker • Clinical • Metastases • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Three- and Seven-month Prostate-specific Antigen Levels as Prognostic Markers for Overall Survival in Metastatic Hormone-sensitive Prostate Cancer: Results from SWOG S1216, a Phase 3 Randomized Trial of Androgen Deprivation Plus Orteronel or Bicalutamide. (PubMed, Eur Urol Oncol) - "The PSA-3mo and PSA-7mo responses were strongly associated with OS; taken with other emerging prognostic biomarkers, these markers may allow for early identification of patients at the highest risk of death, aid with counseling in clinical practice, and permit design of future clinical trials targeting these patients."

Biomarker • Journal • Metastases • P3 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Correlation of body mass index (BMI) with survival outcomes in patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC): Analysis of patient (pt)-level data from SWOG 1216 study. (ASCO 2024) - P3 | "Herein we report the correlation of BMI with survival outcomes from patient level data from phase III study, SWOG 1216 which randomized pts with mHSPC in 1:1 to ADT + bicalutamide or ADT + orteronel. Our results show that as categorized BMI increased, the risk of death decreased in pts with mHSPC. These data warrant external validation in other randomized phase III studies and can help counseling and prognostication of patients with mHSPC in the clinic. Funding: NIH/NCI grants CA180888, CA180819, and in part by Millennium Pharmaceuticals (Takeda Oncology Company)."

Clinical • Metastases • Genetic Disorders • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Obesity • Oncology • Prostate Cancer • Solid Tumor

Bone Pain and Survival Among Patients With Metastatic, Hormone-Sensitive Prostate Cancer: A Secondary Analysis of the SWOG-1216 Trial. (PubMed, JAMA Netw Open) - P3 | "In the SWOG-1216 trial, patients were randomized (1:1) to receive either androgen deprivation therapy (ADT) with orteronel, 300 mg orally twice daily (experimental group), or ADT with bicalutamide, 50 mg orally daily (control group), until disease progression, unacceptable toxic effects, or patient withdrawal. These data suggest prioritizing these patients for enrollment in clinical trials, may aid patient counseling, and indicate that the inclusion of bone pain in prognostic models of MHSPC may be warranted. ClinicalTrials.gov Identifier: NCT01809691."

Clinical • Journal • Metastases • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Musculoskeletal Pain • Oncology • Pain • Prostate Cancer • Solid Tumor

S1216, Phase III ADT+TAK-700 vs. ADT+Bicalutamide for Metastatic Prostate Cancer (clinicaltrials.gov) - P3 | N=1313 | Completed | Sponsor: SWOG Cancer Research Network | Active, not recruiting ➔ Completed | Trial completion date: Oct 2027 ➔ Sep 2025

Trial completion • Trial completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Hormone Therapy, Radiation Therapy, and Steroid 17alpha-monooxygenase TAK-700 in Treating Patients With High-Risk Prostate Cancer (clinicaltrials.gov) - P3 | N=239 | Completed | Sponsor: Radiation Therapy Oncology Group | Active, not recruiting ➔ Completed | Trial completion date: Jun 2029 ➔ Sep 2025

Trial completion • Trial completion date • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

Phase III trial of dose escalated radiation therapy and standard androgen deprivation therapy (ADT) vs. dose escalated radiation therapy and enhanced ADT with orteronel for men with high-risk prostate cancer (NRG/RTOG 1115). (PubMed, Int J Radiat Oncol Biol Phys) - "The addition of orteronel to RT and ADT did not result in significant improvement in any efficacy outcomes, although information was limited by poor drug tolerance and early termination of accrual thus limiting statistical power."

Journal • P3 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Androgen pathway gene expression and response to hormonal therapy in prostate cancer (SWOG S1216). (ASCO 2025) - P3 | " Participants were men with metastatic castration-sensitive prostate cancer (mCSPC) enrolled in SWOG S1216, a phase III randomized multicenter clinical trial of ADT with a CYP17,20 lyase inhibitor (TAK-700) or an androgen receptor inhibitor (bicalutamide). Expression of androgen metabolism genes in primary prostate tumors is associated with response to androgen deprivation therapy and may guide treatment selection in mCSPC."

Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • AKR1C2 • CYP17A1 • HSD17B2

Development and validation of a novel circulating tumor cell response stratification criteria for metastatic castration-resistant prostate cancer clinical trials. (ASCO 2025) - P3 | " We analyzed two phase 3 TAK-700 clinical trials in mCRPC (ELM-PC4, NCT01193244; ELM-PC5; NCT01193257)... CTC-RS is associated with clinical outcome and untethers response from BL CTC burden by using percentage-based criteria, enabling improved evaluation of high CTC burden patients. CTC-RS has modest agreement with BOR and stratifies RECIST-SD patients into responders and non-responders, reflecting the ability to assess the totality of disease. CTC-RS criteria."

Circulating tumor cells • Clinical • Metastases • Tumor cell • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CTCs

The Predictive Role of the Gleason Score in Determining Prognosis to Systematic Treatment in Metastatic Castration-Sensitive Prostate Cancer: A Systematic Review and Network Meta-Analysis. (PubMed, J Clin Med) - "In the overall population, most ARSI combination therapies improved survival outcomes, except for orteronel + androgen deprivation therapy (ADT). In the Gleason score ≥8 subgroup, all ARSI combination therapies improved OS, with rezvilutamide showing the highest probability of being the best treatment for OS (HR 0.48, 95% CI 0.31-0.76, P-scores 0.88). In the Gleason score <8 subgroup, only darolutamide + docetaxel + ADT (HR 0.49, 95% CI 0.29-0.81) and apalutamide + ADT (HR 0.67, 95% CI 0.46-0.98) improved OS. ARSI combination therapy is effective for mCSPC patients with Gleason score ≥8, but further investigation is needed to confirm its efficacy in patients with Gleason score <8."

Journal • Retrospective data • Review • Castration-Sensitive Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Livmoniplimab and budigalimab combination therapy in treating patients with metastatic ovarian granulosa cell tumors: results from dose escalation in a first-in-human study (AIOM 2024) - P1 | "Several agents with different targets, such as pembrolizumab, nirogacestat, orteronel and STM 434, are being evaluated but to date without clinical benefit...She had received 7 prior lines of therapy including doxorubicin, bevacizumab, anastrozole, tamoxifen and carboplatin+paclitaxel... Livmo+budi had promising antitumor efficacy and tolerablesafety profile in pts with metastatic OGC. All enrolled pts showed tumor shrinkage and 1 pt had durable and near-complete response. Since singleagent pembrolizumab exhibited an ORR of 0%(How et al."

Clinical • Combination therapy • Metastases • P1 data • Anemia • Fatigue • Hematological Disorders • Hepatology • Oncology • Ovarian Cancer • Solid Tumor • FOXL2 • TGFB1

Inherited variants in SRD5A genes and response to hormonal therapy in prostate cancer (SWOG S1216) (ESMO 2024) - "Men carrying SRD5A gene variants may experience worse outcomes in response to hormonal therapy, especially when ADT is combined with a selective CYP17,20 lyase inhibitor."

Castration-Sensitive Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • SRD5A1 • SRD5A2 • SRD5A3

Livmoniplimab and budigalimab combination therapy in treating patients with metastatic ovarian granulosa cell tumors: Results from dose escalation in a first-in-human study (AACR 2024) - P1 | "Several agents with different targets, such as pembrolizumab, nirogacestat, orteronel, and STM 434, are being evaluated but to date have not shown clinical benefit...She had received 7 prior lines of therapy including doxorubicin, bevacizumab, anastrozole, tamoxifen, and carboplatin + paclitaxel... Livmo + budi had promising antitumor efficacy and a tolerable safety profile in pts with metastatic OGC, a rare TGF-β signaling-dependent tumor. All enrolled pts with OGC showed tumor shrinkage and 1 pt had durable and near-complete response. Since single-agent pembrolizumab exhibited an ORR of 0% in pts with OGC (How et al."

Clinical • Combination therapy • IO biomarker • Metastases • P1 data • Oncology • Ovarian Cancer • FOXL2 • TGFB1

Three- and Seven-month Prostate-specific Antigen Levels as Prognostic Markers for Overall Survival in Metastatic Hormone-sensitive Prostate Cancer: Results from SWOG S1216, a Phase 3 Randomized Trial of Androgen Deprivation Plus Orteronel or Bicalutamide (ScienceDirect, Eur Urol Oncol) - P3 | N=1,313 | S1216 (NCT01809691) | "A total of 1251 and 1231 patients from the S1216 study were evaluable for PSA-3mo and PSA-7mo, respectively. A PSA-7mo CR was associated with improved OS compared with NR (HR: 0.20; p < 0.0001). A PSA-3mo CR showed a similar association to NR (HR: 0.34; p < 0.0001). The association of a PSA response with survival did not differ by treatment arm at either time point."

P3 data • Prostate Cancer

Three- and Seven-month Prostate-specific Antigen Levels as Prognostic Markers for Overall Survival in Metastatic Hormone-sensitive Prostate Cancer: Results from SWOG S1216, a Phase 3 Randomized Trial of Androgen Deprivation Plus Orteronel or Bicalutamide (ScienceDirect, Eur Urol Oncol) - P3 | N=1,313 | S1216 (NCT01809691) | "A total of 1251 and 1231 patients from the S1216 study were evaluable for PSA-3mo and PSA-7mo, respectively. A PSA-7mo CR was associated with improved OS compared with NR (HR: 0.20; p < 0.0001). A PSA-3mo CR showed a similar association to NR (HR: 0.34; p < 0.0001). The association of a PSA response with survival did not differ by treatment arm at either time point."

P3 data • Prostate Cancer