CBR Polling Shows Rapid Uptake of Darolutamide in mHSPC

The therapeutic landscape for metastatic hormone-sensitive prostate cancer (mHSPC) continues to evolve following the ARANOTE trial (NCT04736199), which demonstrated a robust radiographic progression-free survival (rPFS) benefit with darolutamide (Nubeqa) plus androgen deprivation therapy (ADT) and a favorable tolerability profile.¹^,² In real time, oncologists reacted to these data and gave their opinions.

Across 2025 Case-Based Roundtable (CBR) events, multiple polling questions show a consistent and convergent theme: United States oncologists are increasingly prioritizing a doublet that preserves tolerability, minimizes central nervous system (CNS) liability, avoids chronic steroid exposure, and reduces cytochrome P450 (CYP) drug-drug interaction complexity for older patients with low-volume metastatic disease who are expected to be on therapy for years. Oncologists answered these questions based off of a patient case and case discussion.

CASE SUMMARY

• A 67-year-old man with an active lifestyle presented with urinary retention, fatigue and decreased appetite.
• Medical history: hypertension and hyperlipidemia, both well controlled with medication
• No family history of prostate cancer
• Transrectal ultrasound and biopsy revealed adenocarcinoma of the prostate gland, Gleason score 8 [4+4] with disease in 10/12 cores
• Prostate-specific antigen (PSA), 150 ng/mL; hemoglobin, 9.7 g/dL; absolute neutrophil count, 1.9
• The patient was diagnosed with localized high-grade prostate cancer.
• He underwent robotic radical prostatectomy with subsequent PSA decrease (<0.1 ng/mL).
• CT and bone scans showed no residual disease.
• Thirteen months later: PSA, 35 ng/mL; hemoglobin, 10.3 g/dL; absolute neutrophil count, 1.6
• Imaging: CT and bone scans show multiple enlarged retroperitoneal lymph nodes and 3 metastatic bone lesions (2 in pelvis, 1 in S1 vertebrae)
• Asymptomatic; ECOG performance status, 0
• The patient was diagnosed with metastatic prostate cancer.
• Germline and somatic genetic testing were negative.
• He was referred to a medical oncologist.
• Therapeutic options (including bimodal and trimodal regimens) were reviewed with the patient as part of shared decision making
• He wished to pursue an aggressive treatment approach but would prefer to receive oral treatment and minimizing adverse events is very important to him.

In the first polling question, darolutamide plus ADT was already selected as the second most common preferred doublet, at 25%—ahead of enzalutamide (Xtandi) and apalutamide (Erleada)—despite being the newest androgen receptor pathway inhibitor (ARPI) introduced in this disease state (Polling Question 1). In ARANOTE, darolutamide plus ADT demonstrated a robust rPFS benefit with a favorable tolerability profile compared with ADT alone.^1,2

Polling Question 1. What systemic treatment option are you most likely to recommend for this patient?

In follow-up polling, after clinical data review and case discussion, more than half of respondents (55%) reported they would now be likely to use a darolutamide-based doublet in this same clinical scenario, confirming an adoption signal (Polling Question 2).

Polling Question 2. After the discussion of this case, do you plan on making any changes to your practice with respect to treatment planning and/or management of mHSPC?

The same pattern holds across other dependent choice questions: when oncologists re-evaluate sequencing choices, toxicity trade-offs, and salvage/next-line decisions, the preferences move toward a backbone that leaves options open. Commonly, oncologists now express a “doublet first, keep chemotherapy optional” mentality, which fits directly into the ARANOTE biology and the lived reality of 70-year-old patients with multiple comorbidities. That theme is repeatedly reinforced by polling trajectories across all polling questions. This is notably different from the historic LATITUDE (NCT01715285)/STAMPEDE (NCT00268476) era where chronic prednisone or higher CYP interaction burden was more readily accepted in exchange for early intensification.^3,4

In metastatic castration-resistant prostate cancer–adjacent questions, where another ARPI or radionuclide combination could theoretically be appealing, respondents still do not gravitate toward more toxic or CYP-heavy intensification strategies. The instinct remains: protect tolerability, do not burn future options prematurely, avoid chronic steroids, and avoid cognitive drift or fatigue signal. Again, this is darolutamide-compatible thinking.

Across all polling questions from these CBR sessions, the consistency is striking: oncologists are reframing systemic intensification in HSPC not simply as a question of magnitude of effect, but as a question of how to build a long game plan for patients who may live many years with metastatic disease. In that framework, darolutamide is not emerging as “the new ARPI,” rather a practical ARPI—the one that fits the way oncologists are actually trying to treat older patients in 2025.

_References:

_{1. Saad F, et al. Darolutamide plus androgen deprivation therapy in metastatic hormone-sensitive prostate cancer: ARANOTE. J Clin Oncol. 2024;42:4271-4281.}

_{2. Saad F, et al. ARANOTE: Updated results. ESMO Annual Congress 2024. Abstract LBA68.}

_{3. Fizazi K, et al. Abiraterone plus prednisone in metastatic hormone-sensitive prostate cancer: LATITUDE. N Engl J Med. 2017;377:352-360.}

_{4. James ND, et al. Abiraterone for prostate cancer not previously treated with hormone therapy: STAMPEDE. N Engl J Med. 2017;377:338-351.}