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Darolutamide improves OS in mHSPC

Presented by
Dr Matthew Smith, Massachusetts General Hospital Cancer Center, MA, USA
ASCO GU 2022
Phase 3, ARASENS
In the phase 3 ARASENS trial, the androgen receptor inhibitor darolutamide in combination with androgen deprivation therapy (ADT) and docetaxel improved overall survival (OS) in patients with metastatic hormone-sensitive prostate cancer (mHSPC).

Darolutamide is a highly potent androgen receptor inhibitor that demonstrated improved OS and metastasis-free survival versus placebo in patients with non-metastatic castration-resistant prostate cancer (mCRPC) [1,2]. The current treatment guidelines for mHSPC recommend the addition of docetaxel to ADT in patients who present with M1 disease and are fit for docetaxel.

The ARASENS trial (NCT02799602) evaluated whether darolutamide in combination with standard ADT plus docetaxel would increase OS in patients with mHSPC. The study enrolled 1,306 mHSPC patients with a median age of 67 years. Participants were randomised 1:1 to darolutamide or matching placebo in addition to ADT plus docetaxel. The primary endpoint of the study was OS. Secondary endpoints included time to CRPC, time to pain progression, time to first symptomatic skeletal event, time to initiation of subsequent systemic antineoplastic therapies, and safety. Dr Matthew Smith (Massachusetts General Hospital Cancer Center, MA, USA) presented the study outcomes, which were simultaneously published in The New England Journal of Medicine [3,4].

At the primary data cut-off, darolutamide significantly decreased the risk of death by 32.5% versus placebo (HR 0.68; P<0.0001). Median OS was non-evaluable versus 48.9 months for treatment with darolutamide and placebo, respectively. At 48 months of follow-up, the survival rate was 62.7% and 50.4%, respectively. This improvement in OS was observed even though substantially more patients received subsequent life-prolonging systemic antineoplastic therapy in the placebo arm (75.6%) versus the darolutamide arm (56.8%). Darolutamide also significantly delayed time to CRPC versus placebo (HR 0.36; P<0.0001), time to pain progression (HR 0.79; P=0.01), time to first symptomatic skeletal event (HR 0.71; P=0.02), and time to initiation of subsequent systemic antineoplastic therapy (HR 0.39; P<0.001).

Treatment-emergent adverse events (TEAEs) were similar between the study arms. The incidence of the most common TEAEs (≥10%) were highest during the docetaxel treatment period for both arms, with grade 3/4 TEAEs of 66.1% for darolutamide and 63.5% for placebo, mainly due to neutropenia (33.7% and 34.2%, respectively). TEAEs led to treatment discontinuation in 13.5% of participants in the darolutamide arm and 10.6% of participants in the placebo arm.

“In patients with mHSPC, early treatment combining darolutamide with ADT plus docetaxel significantly increased OS and improved key secondary endpoints versus ADT plus docetaxel alone,” concluded Dr Smith. “Therefore, darolutamide in combination with ADT and docetaxel could become a new standard of care for treatment of patients with mHSPC.”

  1. Fizazi K, et al. N Engl J Med 2019;380:1235–1248.
  2. Fizazi K, et al. N Engl J Med 2020;383:1040–1049.
  3. Smith MR, et al. Overall survival with darolutamide versus placebo in combination with androgen-deprivation therapy and docetaxel for metastatic hormone-sensitive prostate cancer in the phase 3 ARASENS trial. Abstract 13, ASCO GU 2022, 17–19 February.
  4. Smith MR, et al. N Engl J Med 2022;386:1132–1142.


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