Darolutamide Combined with NSD2 Inhibitor: Mechanism of Action
The provided evidence does not contain any information about darolutamide in combination with an NSD2 (Nuclear Set Domain Containing 2) inhibitor for prostate cancer treatment. This combination is not mentioned in any of the current NCCN, ESMO, AUA/SUO guidelines, FDA approvals, or clinical trials provided 1, 2, 3, 4.
What the Evidence Actually Shows About Darolutamide
Established Mechanisms and Combinations
Darolutamide functions as a direct androgen receptor (AR) antagonist that competitively inhibits androgen binding to the AR, blocks AR nuclear translocation, and prevents AR-mediated transcription 3, 5. The drug has a unique chemical structure with high affinity for AR and maintains antagonist activity against mutant AR isoforms (F877L, F877L/T878A, and H875Y/T878A) that confer resistance to enzalutamide 5, 6.
FDA-Approved Combinations
The only evidence-based combinations for darolutamide include:
Darolutamide + ADT + docetaxel for metastatic hormone-sensitive prostate cancer (mHSPC): The ARASENS trial demonstrated 4-year overall survival of 62.7% versus 50.4% with placebo (HR 0.68; P<0.001), representing a 32.5% reduction in risk of death 1, 2, 7.
Darolutamide + ADT for non-metastatic castration-resistant prostate cancer (nmCRPC): The ARAMIS trial showed metastasis-free survival of 40.4 versus 18.4 months compared to placebo (HR 0.41; P<0.001) 2, 3.
Why NSD2 Inhibitor Combination Is Not Addressed
NSD2 inhibitors represent an investigational class of epigenetic modulators that are not part of current standard prostate cancer treatment algorithms 1. No clinical trials, preclinical data, or mechanistic studies regarding this specific combination appear in the provided guideline or research evidence.
Clinical Implications
If you are considering this combination, it would only be appropriate in the context of a clinical trial, as there is no established safety, efficacy, or mechanistic data to support its use in routine clinical practice 1, 2.