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ASCO GU 2025: Concomitant G-CSF Use in Maintaining an Efficacious Dose and Safe Delivery of Docetaxel in Combination with Darolutamide in Patients with Metastatic Hormone Sensitive Prostate Cancer (mHSPC): ARASENS, a Phase 3 Study

(UroToday.com) The 2025 American Society of Clinical Oncology (ASCO) Genitourinary (GU) Annual Symposium held in San Francisco, CA between February 13–15, 2025 was host to a prostate cancer poster session. Dr. Michael Ong presented an ad hoc analysis of the phase III ARASENS trial evaluating concomitant G-CSF use in maintaining an efficacious dose and safe delivery of docetaxel in combination with darolutamide in patients with metastatic hormone sensitive prostate cancer (mHSPC).


In the phase III ARASENS trial, darolutamide, in combination with androgen deprivation therapy (ADT) and docetaxel, significantly reduced the risk of death by 32.5% versus placebo in mHSPC patients, with similar incidences of treatment-emergent adverse events (TEAEs) between groups.1

Neutropenic complications of docetaxel remain a concern in both clinical and real-world studies.2-4 Both ARASENS and PEACE-1 used granulocyte colony stimulating factor (G-CSF) to mitigate the risk of neutropenic complications, but the role and frequency of primary versus secondary G-CSF prophylaxis is debated.5,6 In this study, Dr. Ong and colleagues reported the impact of docetaxel dose intensity and G-CSF use on the safety and efficacy of the ARASENS triplet regimen. 

ARASENS (NCT02799602) is a global, randomized, double-blind, placebo-controlled phase III trial. Patients were randomized to receive darolutamide 600 mg orally twice daily or placebo, with ADT + docetaxel. Baseline characteristics, G-CSF use, safety, overall survival (OS), and time to prostate-specific antigen (PSA) progression at week 24 (for consistency with prior studies)7,8 were analyzed according to docetaxel relative dose intensity (RDI; ≤85% vs >85%), defined as the ratio of docetaxel dose received versus protocol-defined full planned dose (75 mg/m2 × 6 cycles). In total, 1,305 patients were available for analysis in ARASENS; of these, 1,279 received docetaxel therapy and 1,273 had docetaxel RDI data. 

Aside from geographic differences, patient demographics and baseline disease characteristics were mostly consistent between the docetaxel RDI ≤85% and >85% subgroups in both darolutamide and placebo treatment groups.

In both darolutamide and placebo treatment groups, >97% of patients received an efficacious dose of docetaxel (RDI >80%) and over 88% received RDI >85%, indicating that darolutamide does not have an impact on received docetaxel dose intensity. image-1.jpg
Overall, 800/1,279 (63%) patients required docetaxel dose modification, and 556/1,279 (43%) patients required G-CSF, mainly for secondary prophylaxis (>98%). 376/800 (47%) of patients with docetaxel dose modification received G-CSF. The addition of darolutamide did not increase G-CSF use or docetaxel dose modification.Overall, 800/1,279 (63%) patients required docetaxel dose modification, and 556/1,279 (43%) patients required G-CSF, mainly for secondary prophylaxis (>98%). 376/800 (47%) of patients with docetaxel dose modification received G-CSF. The addition of darolutamide did not increase G-CSF use or docetaxel dose modification.
What about G-CSF use by region? Overall and in the Asia Pacific region, a higher rate of G-CSF use was observed for patients with lower vs higher RDI (≤85% vs >85%). G-CSF use was highest in the Asia Pacific patient population compared with the North American and overall populations. G-CSF was primarily used for secondary prophylaxis, independent of region.
What about G-CSF use by region? Overall and in the Asia Pacific region, a higher rate of G-CSF use was observed for patients with lower vs higher RDI (≤85% vs >85%). G-CSF use was highest in the Asia Pacific patient population compared with the North American and overall populations. G-CSF was primarily used for secondary prophylaxis, independent of region.What about G-CSF use by region? Overall and in the Asia Pacific region, a higher rate of G-CSF use was observed for patients with lower vs higher RDI (≤85% vs >85%). G-CSF use was highest in the Asia Pacific patient population compared with the North American and overall populations. G-CSF was primarily used for secondary prophylaxis, independent of region. 2What about G-CSF use by region? Overall and in the Asia Pacific region, a higher rate of G-CSF use was observed for patients with lower vs higher RDI (≤85% vs >85%). G-CSF use was highest in the Asia Pacific patient population compared with the North American and overall populations. G-CSF was primarily used for secondary prophylaxis, independent of region. 3
What about OS and time to PSA progression by docetaxel RDI subgroup? OS was similar in both treatment groups in patients who achieved docetaxel RDI ≤85% or >85% at week 24:

  • Darolutamide group: Median OS was not reached for both ≤85% vs >85% docetaxel RDI subgroups (hazard ratio [HR]: 1.41, 95% confidence interval [CI]: 0.88–2.26)
  • Placebo group: Median OS was not reached vs 45.8 months for the ≤85% vs >85% docetaxel RDI subgroups, respectively (HR: 1.17, 95% CI: 0.80–1.71)

Time-to-PSA progression was also similar between the subgroups with docetaxel RDI ≤85% or >85% at week 24 in both treatment groups:

  • Darolutamide group: Median time-to-PSA progression was not reached for both ≤85% vs >85% docetaxel RDI subgroups (HR: 1.28, 95% CI: 0.71–2.33)
  • Placebo group: Median time-to-PSA progression was 21.7 vs 19 months for the ≤85% vs >85% docetaxel RDI subgroups, respectively (HR: 1.18, 95% CI: 0.81–1.73)

From a safety standpoint, treatment-emergent adverse events leading to docetaxel dose modifications were higher with docetaxel RsDI ≤85% vs RDI >85%. Incidences of grade ≥3 treatment emergent adverse events, including neutropenia and febrile neutropenia, were higher for patients with RDI ≤85% vs RDI >85%. Almost all instances (87/97, 91.3%) of febrile neutropenia were grade 3 in severity. Rates of docetaxel discontinuation were low in all groups, indicating appropriate use of G-CSF allows effective docetaxel administration and that darolutamide does not impact docetaxel tolerability.
Rates of docetaxel discontinuation were low in all groups, indicating appropriate use of G-CSF allows effective docetaxel administration and that darolutamide does not impact docetaxel tolerability.
Dr. Ong concluded as follows:

  • Use of G-CSF with or without dose modification occurred mostly after the first dose of docetaxel, as secondary prophylaxis
  • With appropriate use of G-CSF and docetaxel dose modification, almost all patients (>97%) received an efficacious dose of docetaxel (RDI >80%)
  • Addition of darolutamide to ADT and docetaxel did not increase docetaxel dose modification rates or G-CSF use
  • Although incidences of neutropenia and febrile neutropenia were higher in patients receiving lower vs higher RDI (≤85% vs >85%), rates of discontinuation were comparable
  • Use of G-CSF as primary prophylaxis was negligible, although this may be a consideration for at-risk patients receiving the ARASENS triplet regimen
  • There was no difference in overall survival and time-to-PSA progression between the two RDI subgroups

Presented by: Michael Ong, MD, FRCPC, Medical Oncologist, The Ottawa Hospital Cancer Centre, Ottawa, ON

Written by: Rashid K. Sayyid, MD, MSc – Robotic Urologic Oncology Fellow at The University of Southern California, @rksayyid on Twitter during the 2025 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, CA, Thurs, Feb 13 – Sat, Feb 15, 2025. 

References:
  1. Smith MR, Hussain M, Saad F, et al. Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer. N Engl J Med. 2022; 386(12):1132–42.
  2. James ND, Sydes MR, Clarke NW, et al. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet. 2016; 387(10024):1163–77.
  3. Sweeney CJ, Chen YH, Carducci M, et al. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. N Engl J Med. 2015; 373(8):737–46.
  4. Gravis G, Fizazi K, Joly F, et al. Androgen-deprivation therapy alone or with docetaxel in non-castrate metastatic prostate cancer (GETUG-AFU 15): a randomised, open-label, phase 3 trial Lancet Oncol. 2013; 14(2):149–58.
  5. Fizazi K, Foulon S, Carles J, et al. Abiraterone plus prednison.e added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 × 2 factorial design. Lancet. 2022; 339(10307):1695–707.
  6. Mahil J, Highes C, Patel K et al. Febrile Neutropenia Rates in Men Treated with Docetaxel Chemotherapy for Metastatic Hormone-sensitive Prostate Cancer. Clin Oncol (Royal College of Radiologists). 2016; 28(9):612.
  7. Matsubara N, Chi KN, Ozguroglu M, et al. Correlation of Prostate-specific Antigen Kinetics with Overall Survival and Radiological Progression-free Survival in Metastatic Castration-sensitive Prostate Cancer Treated with Abiraterone Acetate plus Prednisone or Placebos Added to Androgen Deprivation Therapy: Post Hoc Analysis of Phase 3 LATITUDE Study. Eur Urol. 2020; 77(4):494–500.
  8. Chowdhury S, Bjartell A, Agarwal N, et al. Deep, rapid, and durable prostate-specific antigen decline with apalutamide plus androgen deprivation therapy is associated with longer survival and improved clinical outcomes in TITAN patients with metastatic castration-sensitive prostate cancer. Ann Oncol. 2023; 34(5):477–85.