Research in Context

Research in Context is a structured summary that editors at The Lancet’s journals ask all authors to provide when submitting an original research article. Read more

A collaboration with

ARANOTE: darolutamide plus ADT linked with delayed pain and wellbeing decline vs placebo in mHSPC

In an exploratory subgroup analysis, investigators reported the greatest pain and HRQoL benefits among patients with deep PSA responses in this phase 3 trial.

  • Alicia K Morgans, MD; Kunhi Parambath Haresh, MD; Mindaugas Jievaltas, MD; David Olmos, MD; Neal D Shore, MD; Egils Vjaters, MD; et al.

  • April 9, 2026

  • The Lancet Oncology
  • The Lancet Oncology, Volume 27, Issue 5, Pages 614–624
  • 10.1016/S1470-2045(26)00014-8

Share

Evidence before this study

In addition to disease control and survival, reducing pain and maintaining quality of life are important concerns for patients with metastatic hormone-sensitive prostate cancer (mHSPC). According to a literature search of PubMed (last run July 29, 2025, with no date restrictions)—using the search string (apalutamide OR enzalutamide OR darolutamide OR abiraterone) AND ((metastatic) AND (hormone OR castrate OR castration) AND (sensitive OR naive)) AND (prostate cancer) AND (pain OR (quality of life))—patients with mHSPC often have high baseline health-related quality of life (HRQoL), and patients treated with other androgen receptor inhibitors (apalutamide or enzalutamide) typically experience similar time to deterioration in pain and HRQoL as those receiving placebo. The phase 3 ARANOTE study was conducted to assess the efficacy and safety of darolutamide and ADT, to offer flexibility in the treatment of patients with mHSPC with or without docetaxel according to patients’ needs and preferences; measures of pain and HRQoL were included as important additional endpoints to assess the full impact of treatment on patients.

Added value of this study

To our knowledge, darolutamide is the only androgen receptor inhibitor to demonstrate clinically meaningful delays in pain progression and deterioration in overall wellbeing compared with placebo in phase 3 mHSPC studies. In ARANOTE, these benefits were greatest in darolutamide-treated patients who had deep PSA responses, confirming the importance of reaching PSA of less than 0·2 ng/mL in patients with mHSPC.

Implications of all the available evidence

The clinically meaningful benefits of darolutamide in terms of pain and HRQoL outcomes, together with the proven efficacy and safety profile, provide valuable information to help guide treatment decisions in patients with mHSPC.

Source: The Lancet Oncology

Your research deserves a global audience

The Lancet Group reaches millions of clinicians and researchers worldwide.

Publish with The Lancet Group

Related Content

Randomised phase 2 BULLSEYE trial: ¹⁷⁷Lu-PSMA-617 in oligometastatic HSPC

Long-term outcomes and delayed toxic effects remain under investigation, but investigators report the trial suggests ¹⁷⁷Lu-PSMA-617 could delay disease progression in high-risk oligometastatic hormone-sensitive prostate cancer.

  • by Bastiaan M Privé, MD PhD; Walter Noordzij, MD PhD; Constantijn H J Muselaers, MD PhD; Igle J de Jong, MD PhD; Inge M van Oort, MD PhD; Marcel J R Janssen, MD PhD; et al.

  • April 1, 2026

Diagnostic scan images displayed on a radiology monitor.
Abemaciclib plus abiraterone did not improve outcomes in mCRPC, authors report

In this randomised, placebo-controlled study, adding a CDK4/6 inhibitor did not improve outcomes in mCRPC; the authors say further research is needed on possible subgroup benefit.

  • by Matthew Smith, MD PhD; Josep Piulats, MD PhD; Tilman Todenhöfer, MD PhD; Jae-Lyun Lee, MD PhD; José Arranz Arija, MD; Laura Mazilu, MD PhD; et al.

  • November 1, 2025

Medical scan showing a highlighted area in the pelvis.