Using Darolutamide in Clinical Practice for mCRPC


Tomasz M. Beer, MD, FACP, shares his personal experience using darolutamide for patients with CRPC and discusses his approach to patient selection of the drug in the metastatic setting.

Tomasz M. Beer, MD, FACP: My personal experience with darolutamide is in line with the data that are available in the label and primarily in the ARAMIS study. I’ve found darolutamide to be a relatively straightforward drug to prescribe, and I’ve seen the expected adverse effects of a second-generation androgen signaling inhibitor. I haven’t seen cognitive dysfunction, which is in line with what’s been reported with ARAMIS. It’s important to recognize that these patients are also on primary hormonal therapy and some degree of fatigue is expected, some of the complaints that we’re talking about are often present even before prescribing enzalutamide, apalutamide, or darolutamide. But typically, I haven’t seen worsening in those complaints in the patients I’ve prescribed darolutamide to.

To be candid, how do we manage adverse effects? I haven’t encountered a lot of important adverse effects that require management, and that’s true across the board to some extent. Certainly, we see some adverse effects with the other agents out there, and we see some fatigue with enzalutamide where we dose-reduce folks. But these androgen receptor antagonists are generally quite well tolerated, and darolutamide is no exception. I haven’t had a lot of challenges with adverse effects over and above what my patients are already experiencing with the underlying hormonal therapy.

I’m being asked to speculate about which patient types I might prescribe darolutamide to in a metastatic setting, and I find that a very challenging question to answer because the field is complicated. The most likely scenario that I anticipate is if the current randomized trial is successful, then we would see an indication in newly diagnosed metastatic disease in combination with primary hormonal therapy as well as docetaxel chemotherapy. If that trial is successful, that would reinforce what we’re seeing from PEACE1 with abiraterone and docetaxel and would convince me that a triplet combination is the way to go. I see myself embracing that approach with abiraterone in some patients and darolutamide in others. That’s the most likely scenario where I would see indications for darolutamide in the metastatic setting.

The question is, do I agree with the patient participating in the ODENZA trial with darolutamide and enzalutamide and then back on darolutamide. The long and short of it is absolutely. This is an excellent clinical trial that’s asking an important question, and it’s offering appropriate therapy for a patient who has newly diagnosed metastatic disease and has not previously been treated with a next-generation androgen signaling inhibitor. Enzalutamide is FDA approved in this setting, and darolutamide has an ample level of evidence for safety and activity based on other studies that have been done, particularly in nonmetastatic CRPC [castration-resistant prostate cancer]. That’s certainly appropriate in the context of a clinical trial to evaluate it in low-volume metastatic castration-resistant disease.

The 1 thing I would have perhaps done differently in this case is start the 2-drug therapy sooner, at the beginning of hormonal therapy, which then might have made this patient ineligible for ODENZA. But given his course of treatment, and the fact that he was treated with leuprolide alone initially, this made him an excellent candidate for the ODENZA study.

Transcript Edited for Clarity

A 62-Year-Old Man with Metastatic Castration-Resistant Prostate Cancer

Jan. 2017

Initial presentation

  • A 62-year-old man is found to have a firm prostate nodule of 1.5 mm on his routine physical exam

Clinical workup

  • PSA 15.5 ng/mL
  • Family history of prostate cancer
  • Hypertension
  • Digital rectal exam and transrectal ultrasound (TRUS) of the prostate confirm advanced adenocarcinoma of the prostate and Gleason score of 7 (3 + 4)
  • MRI shows lack of metastasis and node involvement (cT2bN0M0)
  • His ECOG PS is 1


  • In Feb. 2017, patient was treated with radical prostatectomy (RP) with nerve sparing surgery and there were no complications.
  • PSA levels go down to 0.3 ng/ml post-operatively but rise to 1.5 ng/ml within 3 months.
  • Patient receives local salvage radiation therapy and PSA goes down to 0.1 ng/ml.
  • PSA levels are checked every 3 months.

Nov. 2017

  • PSA doubling time increased between 2 last check-ups and now PSA is 3.5 ng/ml.
  • Patient undergoes CT and bone scans and is found to 1 metastatic bone lesion.
  • Patient is treated with androgen deprivation therapy (ADT), leuprolide, as continuous treatment and PSA levels go down to 0.2 ng/ml.

May 2018

  • PSA levels rise to 5 ng/ml, but patient is asymptomatic and has adequate organ and bone marrow function.
  • Patient meets the inclusion criteria for the ODENZA trial and is enrolled in it.
  • Patient is treated with darolutamide(1200 mg/day) for 12 weeks, followed by enzalutamide (160 mg/day) for 12 weeks, in addition to continuing on ADT
  • Patient is currently in the extension phase of the study and is being treated with darolutamide.
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