Nubeqa (darolutamide) / Bayer, Orion Corp - LARVOL DELTA

TRIPLE-SWITCH: Docetaxel to Androgen Receptor Pathway Inhibitors in Patients With Metastatic Castration Sensitive Prostate Cancer and Suboptimal PSA Response (clinicaltrials.gov) - P3 | N=830 | Recruiting | Sponsor: Canadian Cancer Trials Group | Not yet recruiting ➔ Recruiting

Enrollment open • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

Androgen receptor-targeted therapies - avoid clinically relevant interactions (PubMed, Aktuelle Urol) - "As a consequence, an impressive decrease in plasma levels of coadministered drugs has to be expected during the use of the potent CYP3A4 inducers apalutamide as well as enzalutamide, in contrast to the mild CYP3A4 inducer darolutamide. As a consequence, abiraterone's spectrum of interaction has to be interpreted differently. As pharmacotherapy approaches, it is helpful to understand the drug biotransformation pathways in more detail, in order to assess the extent of possible interactions that may necessitate the intensification of therapeutic monitoring, or dose modification or any therapeutic switch in time."

Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • AR • CYP3A4

Real-world outcomes among patients with metastatic castration-resistant prostate cancer (mCRPC) receiving guideline-recommended therapies after treatment with 177Lu-PSMA-617: A real-world prostate cancer disease observation (PRECISION) data platform analysis. (ASCO 2025) - "Guideline-recommended therapies included abiraterone, enzalutamide, darolutamide, apalutamide, cabazitaxel, docetaxel, pembrolizumab, sipuleucel-T, niraparib, olaparib, talazoparib, rucaparib, and radium-223. In this real-world analysis, the majority of patients who received guideline-recommended therapies after 177Lu-PSMA-617 achieved at least a PSA50 response, suggesting that 177Lu-PSMA-617 treatment does not preclude response to other subsequent therapies."

Clinical • Metastases • Real-world • Real-world evidence • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • Urology

Intensification of androgen deprivation therapy (ADT) in metastatic hormone sensitive prostate cancer (mHSPC): Patterns of use and impact on outcomes from a large academic medical center. (ASCO 2025) - "Funded by No funding sources reported Background: ADT intensification with docetaxel and/or androgen receptor pathway inhibitors (ARPIs) has survival benefit in mHSPC...Leuprolide (85.3%), relugolix (12.1%) or degarelix (2.7%) were used for ADT. Of those who RI, 80.3% received an ARPI; 62.3% received abiraterone, 14.6% darolutamide, 13.9% apalutamide, and 9.3% enzalutamide... While PFS was longer for those who RI, these pts also had higher volume of disease, higher PSA, and higher rates of de novo disease, likely contributing to poorer OS. Even at a large academic institution, only about half of pts received intensification. Pts not given intensification were older, and patient preference was the most commonly identified reason for not receiving intensification."

Metastases • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Corticosteroid (CS) use and risk of adverse events (AEs) in patients (pts) treated for metastatic hormone-sensitive prostate cancer (mHSPC). (ASCO 2025) - "Funded by Astellas Pharma Inc., Pfizer Inc Background: Treatment (Tx) of mHSPC involves intensifying androgen-deprivation therapy (ADT) with androgen receptor pathway inhibitors (ARPIs; abiraterone, darolutamide, enzalutamide, apalutamide) with/without docetaxel (D)...Multivariable Cox proportional hazards models were used to evaluate the association between CS exposure (binary time-varying variable, defined as ≥1 daily dose of ≥5 mg prednisone-equivalent CS during the follow-up period) and risk of prespecified AEs and death, adjusted for baseline demographic and clinical characteristics, AEs, and healthcare utilization in the 1 year prior to index, as well as average daily dose of CS over all available times prior to index... Among pts with mHSPC, CS exposure was associated with increased risk of nearly all categories of AEs and death. These data can help guide pt counseling and Tx selection."

Adverse events • Clinical • Metastases • Anemia • Castration-Resistant Prostate Cancer • Congestive Heart Failure • Diabetes • Endocrine Disorders • Genito-urinary Cancer • Heart Failure • Hormone Sensitive Prostate Cancer • Infectious Disease • Metabolic Disorders • Oncology • Ophthalmology • Prostate Cancer • Solid Tumor

Efficacy and safety of darolutamide versus abiraterone acetate plus prednisone in combination with ADT for mHSPC: A real-world clinical retrospective study. (ASCO 2025) - "In the treatment of mHSPC, DARO + ADT was associated with significant improvement of clinical outcomes versus AAP+ADT, while their safety is comparable. Time to event end points.NR, not reached. A hazard ratio and 95% CI are based on Cox regression model."

Combination therapy • Real-world • Real-world evidence • Retrospective data • Castration-Resistant Prostate Cancer • Hormone Sensitive Prostate Cancer • Pain • Prostate Cancer

Overall survival following enzalutamide resistance in metastatic castration-sensitive versus metastatic castration-resistant prostate cancer. (ASCO 2025) - "Those with prior use of other ARSIs (abiraterone, apalutamide, or darolutamide) before CRPC were excluded. After ENZA resistance (CRPC 2.0), both mCSPC and mCRPC groups showed similarly poor prognosis, with median OS under 18 months. While taxane-based chemotherapy and alternative ARSIs were commonly used as subsequent treatments, only a small proportion received radionuclide therapy or PARP inhibitors. These findings highlight the urgent need for novel approaches to improve survival in CRPC 2.0."

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

Real world outcomes of darolutamide efficacy and safety in treating non-metastatic and metastatic hormone-sensitive prostate cancer. (ASCO 2025) - "Our real-world data demonstrates the effectiveness and safety of darolutamide in patients with nmHSPC or mHSPC."

Clinical • Metastases • Real-world • Real-world evidence • Fatigue • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Health-related quality of life in metastatic hormone sensitive prostate cancer (mHSPC): Insights from a network meta-analysis of treatment options. (ASCO 2025) - "Darolutamide + ADT showed a significant improvement in time to deterioration in FACT-P total score compared to both ADT monotherapy and apalutamide + ADT, with a favorable trend observed versus both abiraterone + ADT and enzalutamide + ADT. The analysis suggests that darolutamide + ADT may provide HRQoL advantages compared to other ARPIs +ADT. This finding may be an important component of patient-centered treatment decision-making in mHSPC. Results from the HRQoL NMA: Time to deterioration in FACT-P total score.*Hazard Ratio."

HEOR • Metastases • Retrospective data • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Potential risk factors, course of disease, and clinical outcomes of neuroendocrine prostate cancer (NEPC): A retrospective analysis. (ASCO 2025) - "Pts who developed a treatment emergent (t)NEPC in the course of disease (n=39) received ADT monotherapy (41%) or an intensified treatment with an androgen receptor pathway inhibitor (ARPI) (33%), docetaxel (23%) or triple therapy with darolutamide and docetaxel (3%) in the hormone-sensitive stage...At initial diagnosis of NEPC, 93% of the patients were started on 1st line chemotherapy of whom 92% received a platinum-based combination with etoposide... Prognosis of NEPC pts remains poor with rapid progression through multiple lines of treatment and most patients dying within 1 year of diagnosis. This highlights the great need for new therapeutic strategies for pts with NEPC. Baseline characteristics and clinical outcomes of pts with NEPC."

Clinical data • Retrospective data • Genito-urinary Cancer • Neuroendocrine Tumor • Oncology • Prostate Cancer • Solid Tumor

Real-world treatment patterns, sequences, and outcomes in patients with mCRPC in US urology clinics. (ASCO 2025) - "Of the 1,914 patients treated with androgen receptor pathway inhibitors (ARPIs) pre-mCRPC, including enzalutamide (enza), abiraterone (abi), apalutamide, and darolutamide, 95.8%, were treated with ARPI ± ADT. This data indicates the majority of patients used ADT alone pre-mCRPC. ARPI rechallenge was the most common treatment sequence from pre-mCRPC to mCRPC among ARPI exposed patients. Less than half of the patients analyzed received 2L+ therapy."

Clinical • HEOR • Real-world • Real-world evidence • Castration-Resistant Prostate Cancer • Prostate Cancer • Urology

Comparative efficacy and safety of novel androgen receptor inhibitors in nonmetastatic castration-resistant prostate cancer: A systematic review and Bayesian network meta-analysis. (ASCO 2025) - "This study provides a comparative assessment of NSAAs in nmCRPC, highlighting their variable efficacy across different survival outcomes. Apalutamide demonstrated the greatest benefit in OS and TTPP, while darolutamide was most effective for PFS. Enzalutamide showed superior efficacy in improving MFS."

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

Treatment patterns and survival by race among men with metastatic castration-resistant prostate cancer (mCRPC) in the United States: A US electronic medical record database 2020-2023. (ASCO 2025) - "Line of therapy was identified as ARPI, chemotherapy, poly (ADP-ribose) polymerase inhibitors (PARPIs), immunotherapy (pembrolizumab, sipuleucel-T), radiopharmaceuticals (Ra-223, 177Lu-PSMA-RLT), alone or in combination...Overall, ARPI (62%) [abiraterone: 25%; enzalutamide: 24%; apalutamide: 9%; darolutamide 4%] and chemotherapy (22%) [docetaxel 16%; cabazitaxel 6%] were most common first-line treatment (1L Tx) for mCRPC... ARPI and chemotherapy remained the most utilized therapies in mCRPC from 2020 to 2023 in the US. Treatment and survival outcomes did not differ significantly between Whites and AAs in mCRPC. Treatment and survival by race in mCRPC.NE, not evaluable."

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

Safety and efficacy of darolutamide in combination with androgen-deprivation therapy for prostate cancer: A systematic review and meta-analysis of randomized controlled trials. (ASCO 2025) - "Combination therapy of darolutamide and ADT reduced metastatic progression and slowed tumor growth but did not significantly improve overall survival. Adverse events were more common, particularly in CRPC cohort. Longer follow-up studies are needed to assess long-term efficacy and weigh tumor control against adverse event risks."

Combination therapy • Retrospective data • Review • Castration-Resistant Prostate Cancer • Fatigue • Genito-urinary Cancer • Hypertension • Musculoskeletal Diseases • Oncology • Pain • Prostate Cancer • Solid Tumor

Treatment intensification in veterans with metastatic prostate cancer. (ASCO 2025) - "We used multivariable logistic regression to estimate predicted probabilities for treatment intensification (i.e., ADT plus ARPI [abiraterone, enzalutamide, apalutamide, darolutamide] and/or docetaxel) versus ADT alone within six months of metastatic diagnosis. Men with mCSPC had a higher rate of treatment intensification in the VA than prior studies of men with mCSPC in the community; however, rates of treatment intensification remain low, and Black Veterans were still less likely to receive this standard of care despite adjustment for comorbidity, disease characteristics, and other social factors."

Metastases • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Darolutamide plus goserelin for androgen receptor-positive salivary gland cancers: Results of phase 2 study (DISCOVARY). (ASCO 2025) - P2 | "This is the first prospective CAB trial in SGC which has met its primary endpoint. Darolutamide plus goserelin demonstrated clinically meaningful efficacy and a favorable safety profile, suggesting it may be a compelling option before initiating chemotherapy, which can significantly diminish a patient's quality of life. Clinical trial information: NCT05694819."

P2 data • Oncology • Salivary Gland Cancer • AR

Prognostic significance of PSA>0.2 after 6-12 months treatment for metastatic hormone-sensitive prostate cancer (mHSPC) intensified by androgen-receptor pathway inhibitors (ARPI): A multinational real-world analysis of the IRONMAN registry. (ASCO 2025) - "Intensification agents were: abiraterone acetate (576, 44.7%), apalutamide (283, 22.0%), darolutamide (135, 10.5%), or enzalutamide (294, 22.8%), and 122 (8.7%) received docetaxel in addition to ADT-ARPI. IRONMAN provides large real-world data validating the poor prognosis of mHSPC with PSA>0.2 after 6-12 months ADT-ARPI treatment and these patients could be targeted for intensification in future trials. Conversely, PSA<0.02 at 6-12 months defines the best prognosis and may be of interest for de-intensification strategies. OS and PFS outcomes by 12-month PSA strata."

Clinical • Metastases • Real-world • Real-world evidence • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Health-related quality of life (HRQoL) outcomes with darolutamide in the phase 3 ARANOTE trial. (ASCO 2025) - P3 | "To our knowledge, DARO is the first and only androgen receptor inhibitor to demonstrate clinically meaningful delays in deterioration of important patient-relevant HRQoL outcomes vs PBO in men with mHSPC. Patients treated with DARO had improvements in overall well-being (FACT-P total score), social/family well-being, functional well-being, urinary symptoms, and pain. Combined with the efficacy and safety profile, these findings suggest that DARO also confers a positive impact on HRQoL."

Clinical • HEOR • P3 data • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Pain • Prostate Cancer • Solid Tumor

Triplet versus doublet therapy in older patients with metastatic hormone-sensitive prostate cancer: A network meta-analysis. (ASCO 2025) - "The second NMA analyzed seven treatment options, treating different ARAT agents as independent regimens: two triplets (abiraterone or darolutamide) + ADT + docetaxel, three doublets (abiraterone, enzalutamide, or apalutamide) + ADT, ADT + docetaxel, and ADT alone. Triplet therapy of darolutamide + ADT + docetaxel should be prioritized over other treatment options for fit older patients with mHSPC. Further research utilizing real-world effectiveness data is essential to validate this recommendation."

Metastases • Retrospective data • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

TRIPLE-SWITCH (SWOG/CCTG-PR26): A randomized phase III clinical trial for the addition of docetaxel to androgen receptor pathway inhibitors in patients with metastatic castration sensitive prostate cancer (mCSPC) and suboptimal PSA response (NCT06592924). (ASCO 2025) - P3 | "Arm 1 will continue standard ADT + ARPI (abiraterone acetate with prednisone, apalutamide, enzalutamide or darolutamide). Correlative studies will explore the prognostic and predictive value of circulating tumor DNA (ctDNA) and the association between molecular signatures in primary prostate cancer tissue and clinical outcomes. Enrolment has been initiated in January 2025 and is ongoing."

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

Substudy C of the Canadian cancer trials group (CCTG) IND.234: PC_BETS (Prostate Cancer Biomarker Enrichment and Treatment Selection)—A phase II study of darolutamide (DARO) selected by androgen-receptor (AR) circulating tumor DNA (ctDNA) in patients (PTS) with metastatic castration-resistant prostate cancer (mCRPC) after prior AR pathway inhibitors (ARPIs). (ASCO 2025) - P2 | "Sixteen pts (22%) had docetaxel for hormone-sensitive disease and none for mCRPC. Prior ARPI were abiraterone (31/72, 43%), enzalutamide (37/72, 51%), or apalutamide (4/72, 6%)... DARO demonstrates modest activity for unselected mCRPC following ARPIs. ctDNA analysis enriched for pts more likely to benefit from DARO including SPOP alterations, AR amp, and AR mutations L702H and T878A."

Biomarker • Circulating tumor DNA • Clinical • Metastases • P2 data • Anorexia • Castration-Resistant Prostate Cancer • Fatigue • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • AR • SPOP

Darolutamide plus androgen deprivation therapy (ADT) in patients with high-risk biochemical recurrence (BCR) of prostate cancer: A phase 3, randomized, double-blind, placebo-controlled study (ARASTEP). (ASCO 2025) - P3 | "Secondary endpoints include MFS on conventional imaging by BICR, time to CRPC, OS, quality of life, and safety. As of January 2025, 458 patients have been randomized from 220 sites."

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

Phase 3 ARASTEP study to evaluate PSMA PET-CT–detected BCR in prostate cancer (Urology Times) - "Approximately 970 patients across the world are to be randomly assigned 1:1 to receive darolutamide plus ADT or placebo plus ADT for a duration of 24 months. As of April 2025, 616 patients have been randomized...The investigators intend to recruit patients from 243 sites across 23 countries. The study is structured in 4 consecutive periods: screening/baseline, treatment, active follow-up, and long-term follow-up."

Trial status • Prostate Cancer

U.S. FDA approves third indication of darolutamide for patients with advanced prostate cancer (GlobeNewswire) - "Orion’s collaboration partner Bayer announced today that the U.S. Food and Drug Administration (FDA) has approved the oral androgen receptor inhibitor (ARi) darolutamide in combination with androgen deprivation therapy (ADT) for use in patients with metastatic castration-sensitive prostate cancer (mCSPC), which is also known as metastatic hormone-sensitive prostate cancer (mHSPC). The approval is based on positive results from the pivotal Phase III ARANOTE trial....With this approval, darolutamide plus ADT is indicated in the U.S. for the treatment of adult patients with mHSPC either with or without docetaxel."

FDA approval • Hormone Sensitive Prostate Cancer

ARASEC: A Study to Learn How Well Darolutamide Administered Together With Androgen Deprivation Therapy (ADT) Works in Men With Metastatic Hormone-sensitive Prostate Cancer. Results Will be Compared With ADT Alone From a Previously Conducted Study. (clinicaltrials.gov) - P2 | N=223 | Active, not recruiting | Sponsor: Bayer | Trial completion date: Oct 2026 ➔ Jun 2026

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