Apalutamide Yields High Rate of Negative Repeat Biopsies in Men with Prostate Cancer on Active Surveillance

The novel androgen receptor-signaling inhibitor led to negative repeat biopsies after 90 days of treatment among men with very-low risk to favorable intermediate risk prostate cancer on active surveillance.

Treatment with apalutamide (Erleada) monotherapy for 90 days led to negative repeat biopsies in men with very-low risk to favorable intermediate risk prostate cancer on active surveillance, according to phase 2 study findings presented at the Society of Urologic Oncology 21st Annual Meeting.

“Active surveillance is a well-recognized management strategy for men with lower-risk prostate cancer with an overall decrease of overtreatment while maintaining cure rates,” Michael T. Schweizer, MD, associate professor of the Clinical Research Division at Fred Hutch in Seattle, said during a presentation of the results. “A number of professional societies have endorsed active surveillance as the best option for men with very low-risk prostate cancer as a preferred option for those with low-risk disease.”

In addition, he added, for those with favorable, intermediate-risk prostate cancer, active surveillance has also been found to be a safe and effective strategy for mitigating overtreatment.

However, many patients still undergo prostatectomy or radiation following pathologic reclassification, like an increase in tumor volume or Gleason Grade Group. Therefore, strategies to decrease attrition from active surveillance are needed.

Schweizer et al aimed to determine if apalutamide could lead to negative repeat biopsies in active surveillance patients, in turn, leading to decreased rates of pathologic progression and attrition from active surveillance.

The open label, phase 2 study evaluated 90 days of oral apalutamide treatment at a dose of 240 mg daily in men followed on active surveillance. Apalutamide, a novel androgen receptor-signaling inhibitor approved for men with metastatic hormone-sensitive prostate cancer and non-metastatic castration-resistant prostate cancer, was given in the absence of medical/surgical castration.

To be eligible for the study, patients were required to have no more than low-intermediate risk prostate cancer, defined as clinical stage T1c disease, PSA <15 ng/ml, Gleason 3+4 present in ≤50% of one core/site as detected by systematic biopsy or MRI/TRUS fusion guided biopsy, and Gleason 3+3 disease in all other cores.

The percentage of patients with a negative biopsy immediately following the 90-day treatment course served as the primary objective of the study. Secondary objectives included long-term clinical outcomes, quality of life, safety, and exploratory biomarkers of response/resistance.

In total, 23 patients enrolled in the trial, with 22 completing the 90-day treatment regimen with post-treatment biopsy. Fifteen patients (68%) reported with Gleason Grade Group 1 disease, with the remaining with Grade Group 2 disease. Per NCCN criteria, 3 patients (14%) had very low-risk disease, 11 (50%) with low-risk disease, and 8 (36%) with favorable, intermediate-risk disease.

Median PSA was 4.57 (range, 2.4-10.94), with a median of 2 cores involved (range, 1-6). Median time on active surveillance was 10.7 months (range, 0.9-102.7 months).

At 90 days, 13 patients (59%) demonstrated no evidence of residual cancer on post-treatment biopsy following treatment with apalutamide. At 1 year, 7 patients (35%) had no evidence of residual cancer on a second biopsy. All patients had a >50% decline in PSA, and the majority had >90% decline.

Apalutamide appeared well tolerated, consistent with the agent’s known safety profile. The most common adverse events (AEs) included fatigue (grade 1, 70%; grade 2, 9%), gynecomastia (grade 1, 70%), arthralgia/myalgia (grade 1, 30%), dysgeusia (grade 1,, 30%), rash (grade 1, 26%), cognitive impairment (grade 1, 22%), hot flashes (grade 1, 22%), elevated TSH (grade 1, 17%), anorexia (grade 1, 13%), dry skin (grade 1, 13%), decreased libido (grade 1, 13%), pruritus (grade 1, 13%), nausea (grade 1, 9%), and weight loss (grade 1, 9%). One patient experienced grade 3 hypertension, and another patient had grade 3 rash. Of note, both patients remained on the trial after receiving dose reductions.

Schweizer concluded by saying that correlative studies are pending. “We believe, based on these results, that additional randomized studies are warranted with the long-term effects of apalutamide on men enrolled to active surveillance.”


Schweizer MT, True L, Ellis W, et al. Resetting the Active Surveillance Clock: Apalutamide in Lower Risk Prostate Cancer. Presented at: Society of Urologic Oncology 21st Annual Meeting; December 3, 2020. Abstract 1.

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