KEY TAKEAWAYS
- The ENACT Phase 2 clinical trial evaluated the effectiveness and safety of enzalutamide monotherapy in combination with androgen suppression therapy.
- The study’s primary objective was to determine the duration of prostate cancer’s pathological or therapeutic progression.
- The study was conducted at 66 sites in the United States and Canada from June 2016 to August 2020 and involved 227 patients randomly assigned to receive either enzalutamide plus AS or AS alone.
- The administration of enzalutamide resulted in a significant reduction of 46% in the likelihood of prostate cancer progression compared to Active Surveillance.
- Enzalutamide also resulted in a decrease in the proportion of cores that tested positive for cancer and a delay in PSA progression.
- The prevailing untoward incidents observed during the administration of enzalutamide were fatigue (55.4%) and gynecomastia (36.6%).
There is a paucity of published literature that prospectively evaluates pharmacological interventions that may potentially retard the progression of prostate cancer in patients who are undergoing active surveillance (AS). This study aimed to evaluate the effectiveness and safety of enzalutamide monotherapy in combination with androgen suppression therapy compared to androgen suppression therapy alone in individuals diagnosed with low or intermediate-risk prostate cancer. The ENACT study was an open-label and randomized phase 2 clinical trial. It was conducted at 66 United States and Canada sites from June 2016 to August 2020. Patients who met the eligibility criteria were those 18 or older, had been diagnosed with histologically confirmed localized prostate cancer of low or intermediate risk within six months of screening, and were currently undergoing active surveillance. The subjects were observed for one year of therapy and a maximum of two years of post-treatment monitoring. The analysis of data was performed in February of the year 2021. The participants were randomly assigned in a 1:1 ratio to receive either enzalutamide monotherapy at 160 mg for one year or continue with active surveillance, per their cancer risk stratification and follow-up biopsy type.
The study’s principal objective was to determine the duration of prostate cancer’s pathological or therapeutic progression. Pathological progression was defined as an increase of at least one primary or secondary Gleason pattern or a rise of at least 15% in cancer-positive cores. Therapeutic progression was the earliest instance of primary therapy for prostate cancer. The study’s secondary endpoints comprised the frequency of a negative biopsy outcome, the proportion of cores positive for cancer, and the frequency of a subsequent increase in serum prostate-specific antigen (PSA) levels at 1 and 2 years, along with the duration until PSA progression. Safety was evaluated by monitoring adverse events. The study involved 227 patients randomly assigned to receive either enzalutamide plus AS or AS alone. The baseline characteristics of the patients were comparable between the two treatment groups. The mean age of the patients was 66.1 years, with a standard deviation of 7.8. The ethnic distribution of the patients was as follows: 1 Asian individual (0.4%), 21 Black or African American individuals (9.3%), 1 Hispanic individual (0.4%), and 204 White individuals (89.9%). The administration of Enzalutamide resulted in a significant reduction of 46% in the likelihood of prostate cancer progression compared to Active Surveillance (hazard ratio, 0.54; 95% CI, 0.33-0.89; P = .02). In comparison to ankylosing spondylitis (AS), the likelihood of obtaining a negative biopsy result was 3.5 times greater.
The administration of enzalutamide resulted in a notable decrease in the proportion of cores that tested positive for cancer and the probability of a subsequent increase in serum PSA levels after one year of treatment. However, there was no significant variation observed after two years. The administration of enzalutamide resulted in a noteworthy 6-month delay in PSA progression compared to AS. The hazard ratio was 0.71, with a 95% confidence interval ranging from 0.53 to 0.97, and the P= 0.03. The prevailing untoward incidents observed during the administration of enzalutamide were fatigue (62 [55.4%]) and gynecomastia (41 [36.6%]). Three mortalities were observed among the subjects in the enzalutamide cohort; however, none were under the administration of the investigational medication at the time of their demise. There were no fatalities deemed to be associated with the treatment. Based on the findings of this randomized clinical trial, it can be concluded that enzalutamide monotherapy was well-tolerated and exhibited a significant treatment response in patients diagnosed with localized prostate cancer of low or intermediate risk. Enzalutamide could serve as an alternative therapeutic approach for individuals undergoing androgen deprivation therapy to manage prostate cancer.
Source : https://pubmed.ncbi.nlm.nih.gov/35708696/
Clinical Trail: https://clinicaltrials.gov/ct2/show/NCT02799745
Shore ND, Renzulli J, Fleshner NE, Hollowell CMP, Vourganti S, Silberstein J, Siddiqui R, Hairston J, Elsouda D, Russell D, Cooperberg MR, Tomlins SA. Enzalutamide Monotherapy vs Active Surveillance in Patients With Low-risk or Intermediate-risk Localized Prostate Cancer: The ENACT Randomized Clinical Trial. JAMA Oncol. 2022 Aug 1;8(8):1128-1136. doi: 10.1001/jamaoncol.2022.1641. Erratum in: JAMA Oncol. 2022 Aug 1;8(8):1225. PMID: 35708696; PMCID: PMC9204619.
