ESMO 2022: Quality of Life and Patient-relevant Endpoints With Darolutamide in the Phase 3 ARASENS Study

( The 2022 European Society of Medical Oncology (ESMO) annual meeting featured a prostate cancer session, including a presentation by Dr. Karim Fizazi discussing quality of life and patient-relevant endpoints with darolutamide in the phase 3 ARASENS study.

In ARASENS, darolutamide + androgen-deprivation therapy (ADT) + docetaxel significantly reduced risk of death by 32.5% vs placebo + ADT + docetaxel (HR 0.68, 95% CI 0.57–0.80) in patients with metastatic hormone-sensitive prostate cancer (mHSPC).1 Given the potentially long treatment duration, the impact of darolutamide + ADT + docetaxel on patient-relevant endpoints is important to assess.

 In ARASENS, patients were randomized 1:1 to darolutamide 600 mg twice daily or placebo + ADT + docetaxel:


ESMO 2022 ARASENS QoL_Karim Fizazi_0 


Patient-relevant endpoints were all-cause and prostate cancer related death, time course of adverse events of special interest, and quality of life based on time to worsening of disease-related physical symptoms.

In the safety analysis set (n=1,302), the darolutamide + ADT + docetaxel arm (n = 652) had fewer all-cause deaths (35.1% vs 46.8%) and prostate cancer related deaths (26.1% vs 36.0%) vs the placebo + ADT + docetaxel arm (n = 650). Most patients had high baseline quality of life scores, and had no pain or only mild pain at baseline (81%):


ESMO 2022 ARASENS QoL_Karim Fizazi_1 


Despite longer treatment exposure with darolutamide vs placebo (median 41.0 vs 16.7 months), overall adverse event incidence was similar in the two arms. Cumulative incidences of falls (darolutamide 6.6% vs placebo 4.6%; HR 1.05, 95% CI 0.65-1.69), fractures (darolutamide 7.5% vs placebo 5.1%; HR 1.09, 95% CI 0.70-1.70), fatigue (darolutamide 33.1% vs placebo 32.9%; HR 0.95, 95% CI 0.79-1.15) and mental impairment were similar between arms. Fatigue and rash (darolutamide 16.6%, placebo 13.5%) appeared predominantly in treatment months 1–3 and incidence decreased rapidly thereafter. The incidence of cardiac disorders was constant over time and similar between arms (darolutamide 10.9%, placebo 11.7%). Incidence of hypertension was 13.7% vs 9.2%, also with similar distribution over time. Time to worsening of disease-related physical symptoms and pain interference were maintained with the addition of darolutamide in the overall population:


ESMO 2022 ARASENS QoL_Karim Fizazi_2 


In patients with moderate or severe baseline pain, there was a trend of delaying times to worsening of disease-related physical symptoms and pain interference with darolutamide versus placebo (post hoc exploratory analysis):


ESMO 2022 ARASENS QoL_Karim Fizazi_3 


Time to mental impairment, time to rash, time to cardiac disorder, and time to hypertension are as follows:


ESMO 2022 ARASENS QoL_Karim Fizazi_4 


Dr. Fizazi concluded his presentation discussing quality of life and patient-relevant endpoints with darolutamide in the phase 3 ARASENS study with the following take-home messages:

  • Early treatment intensification with darolutamide + ADT + docetaxel improved patient-relevant endpoints, with reduced all-cause and prostate cancer related deaths and similar incidences and time course for most adverse events of special interest vs placebo + ADT + docetaxel, notably with no increase in cardiac disorders
  • Quality of life was maintained over time, and darolutamide had no adverse impact on quality of life, including in patients with poor prognosis
  • Darolutamide in combination with ADT and docetaxel sets a new standard of care for treatment of mHSPC

Presented by: Karim Fizazi, MD, Ph.D., is a medical oncologist at Gustave Roussy, and a full professor in Oncology at the University of Paris-Saclay in Villejuif, France.

Co-Authors: M.R. Smith2, M. Hussain3, F. Saad4, C. Sternberg5, E.D. Crawford6, J.B. Aragon-Ching7, S. Thiele8, S. Kapur9, A.F. Mohamed10, S. Srinivasan11, R. Li11, I. Kuss12, H. Joensuu13, B. Tombal14



  1. Smith MR, Hussain M, Saad F, et al. Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer. N Engl J Med. 2022 Mar 24;386(12):1132-1142.

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