EMBARK Trial: Combination-therapy is better.

[janebob99]

This chart compares the risk of developing metastasis from prostate cancer, after 5 years from curative treatment, between three different arms of the EMBARK study (published in 2023):

(1) Lupron monotherapy;

(2) Enzalutamide monotherapy; and

(3) Enzalutamide + Lupron combination therapy.

The cohort was men with PCa, average age = 69, PSA = 5, after curative treatment (RP or RT).

This chart shows significant differences between the three arms. Lupron monotherapy had the greatest risk of developing metastasis after 5 years (a 28.6 %), compared to a 20.0% risk for Enzalutamide monotherapy. The combination of Enzalutamide + Lupron had the lowest risk (12.7%). p < 0.001 (N=1068).

Combinations of Lupron (or Orgovx, etc.) with other 2nd-generation Anti-Androgens (ARSIs), such as darolutamide and apalutamide, might give similar results.

Ref: pubmed.ncbi.nlm.nih.gov/378...

[maley2711]

I would clarify that this is for men who accepted these treatments for BCR...not for all men who had "curative" treatments.

[Lui22]

What as this treatment indefinite (ie did they take the drugs for the rest of their lives, or for a certain period of time)?

[janebob99 in reply to Lui22]

Good question.

Here's what the report say s(treatment was continued for a minimum of 37 weeks, some longer):

"Enzalutamide (at a dose of 160 mg) or placebo was administered orally once daily with or without food, and leuprolide (at a dose of 22.5 mg) was given as a single intramuscular or subcutaneous injection every 12 weeks. Treatment was suspended at week 37 if the PSA level was less than 0.2 ng per milliliter and was restarted when the PSA level was at least 5.0 ng per milliliter (if the patient had not had previous radical prostatectomy) or at least 2.0 ng per milliliter (if the patient had previously had radical prostatectomy). Patients continued to receive their assigned treatments until imaging-based disease progression (confirmed by central review), an unacceptable adverse event, seizure, or death occurred, nonadherence due to protocol violation was documented, or the patient or physician decided to discontinue the regimen."

[Justfor_ in reply to janebob99]

After the 37 weeks, those with a PSA decline to <0.2 could take a vacation. For some very fortunate ones, this vacation lasted for the 5 years monitoring period. They are now trying to identify what is so different with these special cases where 8-9 months of treatment can prove so effective.

[Mgtd]

Any ideas as to why if the results were so dramatically reduced why it is not the standard of care?

[janebob99 in reply to Mgtd]

Good question.

These results just came out in 2023. It takes many years for the providers to adopt new guidelines.

I think the overall trend in prostate cancer is now "treatment intensification", i.e., doublet or triplet therapy.

"Hit it hard and early" is the new mantra, rather than "try one drug, and if it fails, then try another".

[conbio]

For further perspective from the article:

Adult patients with prostate cancer who had had biochemical recurrence after local therapy were eligible if at the time of the initial biopsy before primary definitive therapy they had histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation, signet-cell features, or small-cell features. Patients also had to meet the following criteria at screening: high-risk disease (defined as a PSA doubling time of ≤9 months and a PSA level of ≥2 ng per milliliter above nadir after radiation therapy or ≥1 ng per milliliter after radical prostatectomy with or without postoperative radiation therapy), a serum testosterone level of at least 150 ng per deciliter, and an Eastern Cooperative Oncology Group performance-status score of 0 or 1 (on a 5-point scale, with higher scores indicating greater disability).

Patients were excluded if they had undergone previous cytotoxic chemotherapy, had a history of seizure or a condition that may confer a predisposition to seizure, showed evidence of distant metastatic disease on conventional imaging (e.g., computed tomography [CT], magnetic resonance imaging [MRI], or bone scans), or if after radical prostatectomy they were considered by the investigator to be a candidate for salvage radiation therapy. Patients who received previous hormonal therapy were excluded, except for the following indications: neoadjuvant or adjuvant therapy at the time of definitive radiation therapy for no more than 36 months and at least 9 months before randomization or a single dose or short course (≤6 months) of hormonal therapy administered for rising PSA levels at least 9 months before randomization.