Lancet Oncol: efficacy of progressive metastatic castration-resistant prostate cancer with continued application of enzalutamide

Although androgen deprivation therapy is usually long-term in patients with metastatic prostate cancer, second-generation hormone therapy is usually stopped
before subsequent treatment.
The study was designed to evaluate the efficacy
of continued use of enzalutamide after the progression of metastatic castration-resistant prostate cancer (mCRPC) treated with docetaxel and prednisolone.

PRESIDE is a double-phase, double-blind, randomized, placebo-controlled Phase 3b study conducted in multiple European countries that enrolled open-label enzalutamide (160 mg/day oral) in patients with histically confirmed prostate adenocarcinoma without neuroendocrine differentiation or small cell features with serum testosterone concentrations ≤ 1.
73 nmol/L, androgen deprivation therapy with luteinizing hormone-releasing hormone agonists or antagonists, or bilateral orchiectomy
。 At week 13, patients are assessed
for radiologic or prostate-specific antigen (PSA) progression.
Patients with a drop in PSA at week 13 and subsequent progression were screened and recruited into phase P2 to receive up to 10 courses of docetaxel + prednisolone, and then randomized (1:1) into two groups to receive oral enzalutamide or placebo
.
The primary endpoint was progression-free survival for all patients in stage P2
.

From December 1, 2014 to February 15, 2016, Phase P1 screened 816 patients, of whom 688 were recruited and 687 received open-label enzalutamide
.
In phase P2, 271 patients were randomized to enzalutamide (n=136) or placebo (n=135).

As of 30 April 2020, median progression-free survival in the enzalutamide and placebo groups was 9.
5 months and 8.
3 months, respectively (HR 0.
72, p=0.
027).

The most common grade 3 treatment-related adverse effects were neutropenia (enzalutamide versus placebo: 13 versus 9 percent) and fatigue (7 versus 4 percent).

The most common grade 4 treatment-related adverse effect was neutropenia (17 versus 21 percent).

Sixty-seven (49%) and 52 (39%) patients in the enzalutamide and placebo groups, respectively, experienced serious treatment-related adverse effects
.
Two of the 13 deaths in the enzalutamide group were considered to be docetaxel-related, while 1 of the seven deaths (14%) in the placebo group were docetaxel-related
.

In summary, the trial achieved its primary endpoint, indicating that after the progression of docetaxel + prednisolone treatment for metastatic castration-resistant prostate cancer, continued enzalutamide combined with docetaxel + androgen deprivation therapy can delay disease progression compared with docetaxel + androgen deprivation therapy alone
.

Original source:

Axel S Merseburger, et al.
Continuous enzalutamide after progression of metastatic castration-resistant prostate cancer treated with docetaxel (PRESIDE): an international, randomised, phase 3b study.
Lancet Oncol.
October 17, 2022.
https://doi.
org/10.
1016/S1470-2045(22)00560-5