Continuous Enzalutamide Shows Benefit in Previously Treated mCRPC

Continuous Enzalutamide Shows Benefit in Previously Treated mCRPC

Results from a phase 3 study show that continuous enzalutamide maintenance therapy reduces the risk of disease progression in certain patients with metastatic castration-resistant prostate cancer.

According to the results published in The Lancet Oncology.1

Findings from the 2-period, multinational, double-blind, randomized, placebo-controlled, phase 3b PRESIDE study (NCT02288247) showed that in the 136 patients who received 160 mg enzalutamide plus 75 mg/mtwo of docetaxel and 10 mg of prednisone had a significant improvement in the risk of its progression compared to 135 with placebo and the same amount of docetaxel and prednisone.

The median progression-free survival (PFS) was 9.5 months (95% CI, 8.3-10.9) in the enzalutamide group compared with 8.3 months (95% CI, 6.3- 8.7) in the placebo group (HR 0.72; 95% CI 0 53–0 96, P = 0.027). Additionally, 74% (n=93) of patients in the enzalutamide group experienced overall disease progression compared to 76% of patients in the placebo group. Enzalutamide was also favored over placebo in patients who also had bone and soft tissue disease progression at 26% vs. 27% and 26% vs. 33%, respectively. However, more patients had unequivocal clinical progression on enzalutamide, 14%, compared to placebo patients, 10%, who progressed.

“PRESIDE provides evidence that the concomitant administration of enzalutamide and docetaxel could serve as a treatment option for patients who progress on enzalutamide alone,” the researchers explained in their evaluation of the results.

Finally, 271 patients with mCRPC were randomized to receive enzalutamide maintenance plus chemotherapy or placebo. Eligible patients had to have histologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features, and serum testosterone concentrations of 1.73 nmol/L or less. These patients must also have progressed during treatment with androgen deprivation therapy with a luteinizing hormone-releasing hormone agonist, antagonist, or after bilateral orchiectomy.

Progression at study entry was defined as three observed increases in prostate-specific antigen (PSA) concentrations, with 1 week or more between each increase, or a PSA value of 2 ng/mL or greater. Patients were considered to have metastatic disease if at least two bone lesions (assessed by bone scan) or soft tissue disease (assessed by CT or MRI) were documented. Exclusion criteria included whether patients were previously using aminoglutethimide, ketoconazole, abiraterone acetate, enzalutamide, or cytotoxic chemotherapy, antiandrogens, 5-α reductase inhibitors, estrogens, or opioid analgesia 4 weeks prior to initiation of enzalutamide.

Then, 136 patients were assigned to enzalutamide and 135 were assigned to placebo with the median age of patients in the treatment arm being 71 years and 69 years in the placebo arm. In the study group, 50% of patients had an ECOG performance score of 1 and 50% in the placebo group had an ECOG score of 0. At diagnosis, 56% of patients in the enzalutamide group had a Gleason score of 8 or higher compared to 57% in the placebo arm. The location of metastases was bone, soft tissue, or bone and soft tissue in the study arm and placebo arm in 42% vs. 35%, 21% vs. 18%, and 37% vs. 47%, respectively.

The responses of this group of patients were favored by the enzalutamide patients, and even more so in the overall response rate (ORR) of patients with soft tissue disease by 41% compared to 39% in the enzalutamide group. of placebo. Enzalutamide was also associated with a significant reduction in the risk of PSA progression (HR, 0.58; 95% CI, 0.41–0.82, P = 0.0021). Additionally, in the enzalutamide group, the median time to PSA progression was 8.4 months (95% CI, 8.2–9.0) compared with 6.2 months (95% CI, 5.4 –8.3) in the placebo group.

“Although the PRESIDE enzalutamide group had higher levels of treatment-emergent serious adverse events than the placebo group, the overall safety findings of the trial are consistent with those of previous studies,” the researchers noted when looking at adverse events ( EA) associated with enzalutamide although its efficacy is observed in this patient population.

Overall, each study arm had a similar overall incidence of grade 3 treatment-emergent AEs (TEAEs) at 38% in the enzalutamide arm and 37% in the placebo arm, and 24% of patients in the enzalutamide arm. the study arm experienced a grade 4 TEAE compared to 25% in the placebo group. The most common TEAEs in the enzalutamide group vs. the placebo group included neutropenia (13% vs. 9%), asthenia (7% vs. 4%), and the most common grade 4 TEAE was neutropenia (17% vs. twenty-one %). Other notable TEAEs in grades 1-2 in the enzalutamide arm vs. placebo arm also included alopecia (30% vs. 27%), fatigue (27% vs. 18%), and docetaxel-related TEAEs (32% vs. 36%).

Reference:

Merseburger AS, Attard G, Åström L, et al. Enzalutamide continued after progression of metastatic castration-resistant prostate cancer treated with docetaxel (PRESIDE): an international, randomized, phase 3b study. Oncol lancet. 2022 November; 23(11): 1398-1408. doi: 10.1016/S1470-2045(22)00560-5

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