Active surveillance (AS) has been shown to be a safe and effective means for men with lower risk prostate cancer to delay or avoid definitive local therapy. However, many patients still undergo prostatectomy or radiation following pathologic reclassification (e.g. increased tumor volume or Gleason Grade Group) and strategies to decrease attrition from AS are needed. We hypothesized that apalutamide, a novel androgen receptor (AR)-signaling inhibitor approved for men with metastatic hormone-sensitive prostate cancer and non-metastatic castration-resistant prostate cancer, would decrease rates of pathologic reclassification due to downstaging low grade tumors.

This was an open label, Phase II study testing 90-days of apalutamide 240 mg daily by mouth in men followed on active surveillance. Apalutamide was given in the absence of medical/surgical castration. Patients were required to have no more than low-intermediate risk prostate cancer, which was defined as: i) clinical stage T1c disease, ii) PSA <15 ng/ml, iii) Gleason 3+4 present in ≤50% of one core/site as detected by systematic biopsy or MRI/TRUS fusion guided biopsy, iv) and Gleason 3+3 disease in all other cores.  The primary objective was to determine the percentage of patients with a negative biopsy immediately following the 90-day treatment course. Secondary objectives were to assess long-term clinical outcomes, quality of life, safety and evaluate exploratory biomarkers of response/resistance.

Twenty-three patients enrolled and 22 completed 3-months of apalutamide with post-treatment biopsy. One patient dropped out pre-biopsy given his desire to limit clinic exposure during the SARS-COV2 pandemic. Fifteen (65%) had Gleason Grade Group 1 disease and all others had Grade Group 2 disease. Three (13%) had very low-risk disease per NCCN criteria. Of 22 evaluable patients, 13 (59%) had no evidence of residual cancer on post-treatment biopsy. Seven of 19 (37%) patients had no evidence of residual cancer on a second biopsy one year after enrolling. All patients had >50% decline in PSA while on apalutamide. Apalutamide was well tolerated and adverse events were generally consistent with apalutamide’s known safety profile. Side effects associated with AR-signaling inhibition quickly resolved following completion of the study. One patient had grade 3 hypertension and another had grade 3 rash. Both of these patients were able to remain on study following dose reductions.

The negative repeat biopsy rate following 90-days of apalutamide monotherapy was high in men with prostate cancer being followed on active surveillance. Apalutamide was safe and well tolerated in this patient population, with side effects due to AR-signaling inhibition quickly resolving following treatment. Randomized studies evaluating the long-term effects of apalutamide in men enrolled on AS are warranted.