Tolerability and treatment response to darolutamide in patients with nmCRPC in the phase III ARAMIS trial

[tango65]

Darolutamide was well tolerated by most patients. Effectiveness related to the PSA decline from baseline.

oncologypro.esmo.org/meetin...

[cesces]

What's nmCRPC

[tango65 in reply to cesces]

non metastatic castration resistant prostate cancer.

[Hidden in reply to cesces]

It's basically an invented state since metastases are defined as only existing if you can see them on a conventional T99 bone scan, CT or MRI.

If you can only see them on one of the more advanced sensitive PET CT scans such as Axumin or PSMA PET, they don't count as metastases.

I think this is bad for those of us who are defined as metastatic since we are not technically approved for this medication.

My doctor hasn't been clear with me whether he could/would prescribe it for me.

[tango65 in reply to Hidden]

He could if you never had metastases diagnosed by Ct and/or bone scan or if the doctor decided to push hard for it. It may help if the medical center or the cancer center has an office dedicated to do this kind of fighting with the insurance companies and medicare.

[Hidden in reply to tango65]

I have had mets diagnosed by CT and T-99 bone scan. I'm being treated at the VA.

I have heard of metastatic guys getting Darolutamide if the S/Es of Xtandi were too much for them to handle.

[tango65 in reply to Hidden]

I hope you will be able to get it if you need it.

Best of luck.

[j-o-h-n]

I asked these two, Chicho Frumboli & Juana Sepulveda and they too don't know what the hell is going on.....

Good Luck, Good Health and Good Humor.

j-o-h-n Tuesday 10/06/2020 5:37 PM DST

[SPEEDYX in reply to j-o-h-n]

But can tango65 really tango

[tango65 in reply to SPEEDYX]

No

[SPEEDYX in reply to tango65]

That's ok I can't run anymore!!!

[j-o-h-n in reply to tango65]

But you sure can tangle.........

Good Luck, Good Health and Good Humor.

j-o-h-n Tuesday 10/06/2020 9:08 PM DST

[tango65 in reply to j-o-h-n]

yeah, like in be aware 2 Tangos approaching fast.....

[j-o-h-n in reply to tango65]

They're called tangelos.....(with pits)....

Good Luck, Good Health and Good Humor.

j-o-h-n Tuesday 10/06/2020 11:03 PM DST

[MateoBeach]

Good news on Daro. Tickle me ESMO. 😎

[GP24]

I just came across this interesting fictive case presentation by Dr. Iwona Skoneczna:

The patient was treated with radical prostatectomy + extended lymph node dissection (ePLND). Postoperative PSA was 0.03 ng/ml.

One year later the PSA rose to 0.18 ng/ml and the patient received salvage radiation therapy which resulted in an undetectable PSA.

Again 1 year later the PSA increased to 1.3 ng/ml (N0 M0 on bone scan and CT). He started androgen deprivation therapy (ADT) and PSA decreased to 0.09 ng/ml.

Follow-up information today, 2 years after initiation of ADT:

PSA: 4.8 ng/ml

PSA doubling time: 5 months

Serum testosterone: 18 ng/dl

Bone and CT scan: negative for metastasis

Dr. Iwona Skoneczna recommended Darolutamide in this case providing the following explanation:

We have 3 live-prolonging options for this patient, who experienced M0 CRPC with a short PSADT: apalutamide, darolutamide and enzalutamide [1-3]. As most men at this stage, he is asymptomatic and willing to control the relapsing cancer, while minimizing treatment-related adverse events. With darolutamide having negligible blood-brain barrier penetration, he may have the lowest potential for central nervous system-related side effects, a low chance of significant fatigue (<0.5%), only 5% risk of falls, less cognitive changes (memory impairment and disturbances in attention) and no risk of seizures, so he may continue his occupational activity in the high mountains. Importantly, darolutamide inhibits both wild-type and mutant AR and retains its activity against AR mutations currently known to cause resistance to enzalutamide and apalutamide, which may be of additional value [4].

References:

Small EJ, et al. Final survival results from SPARTAN, a phase III study of apalutamide versus placebo in patients with non-metastatic castration-resistant prostate cancer. J Clin Oncol 2020;38(Suppl 15):abs.5516

Fizazi K, et al. Overall survival results of phase III ARAMIS study of darolutamide added to androgen deprivation therapy for non-metastatic castration-resistant prostate cancer. J Clin Oncol 2020;38(Suppl 15):abs.5514

Sternberg CN, et al. Final overall survival from PROSPER: a phase III, randomised, double-blind, placebo-controlled study of enzalutamide in men with non-metastatic castration-resistant prostate cancer. J Clin Oncol 2020;38(Suppl 15):abs.5515

Fizazi K, et al. Clinical development of darolutamide: a novel androgen receptor antagonist for the treatment of prostate cancer. Clin Genitourin Cancer 2018;16(5):332-40

If you just have CT and bone scan available, this is a common recurrence for a patient. However, I would prefer a PSMA or Cholin PET/CT and then radiate the detected metastases.

[tango65]

it seems better tolerated than the other anti androgens. Enza and apa are practically the same drug.