Tolerability of Metastasis-Directed Stereotactic Body Radiotherapy with Short-Course Triple-Agent Androgen Annihilation Therapy in Recurrent Oligometastatic Prostate Cancer: Secondary Analysis of a Phase II Study.

Abstract

A majority of patients with oligometastatic prostate cancer experience relapse within 12 months of metastasis-directed therapy. Intense, triple-agent androgen annihilation therapy (AAT) with leuprolide, abiraterone acetate plus prednisone (AAP), and apalutamide may improve efficacy, but long courses of AAT have been shown to be associated with increased rates of grade≥3 toxicity. The purpose of this secondary analysis of this study is to characterize the tolerability of a short, six-month course of AAT added to metastasis-directed therapy. All 28 patients enrolled on this phase II study were included in this analysis. All patients had oligometastatic prostate cancer after initial radical prostatectomy, defined by the presence of 1-5 extrapelvic metastases on prostate-specific membrane antigen (PSMA) PET/CT. Patients were started on six months of AAT. After the first month, patients received stereotactic body radiotherapy (SBRT) in 1, 3, or 5 fractions to metastases with or without radiotherapy to the prostate bed and pelvic lymph nodes. Physician-scored toxicities were graded according to Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0. Median follow-up time was 11.4 months. Twenty patients (71.4%) completed AAT with all three agents. Six patients (21.4%) completed six months of therapy but discontinued at least one agent [4 patients (14.3%) discontinued apalutamide, 1 patient (3.6%) discontinued AAP, and 1 patient (3.6%) discontinued both apalutamide and AAP]. Two patients (7.1%) withdrew from the trial due to adverse events and did not complete therapy. Grade 2 and grade 3 toxicity rates from AAT were each 21.4%. Of the 6 cases of grade 3 toxicity, 3 were skin rashes, 2 were hypertension, and 1 was hepatic toxicity. At the time of SBRT, 1 patient had withdrawn from the study and 1 patient declined radiation therapy. All 26 remaining patients completed SBRT. Grade 2 and grade 3 toxicity rates from SBRT were 7.7% and 0%, respectively. A majority of patients were able to tolerate and complete AAT in combination with metastasis-directed SBRT. Some patients experienced acute grade 3 toxicities, the most common being drug-related skin rashes and hypertension. While efficacy data are needed to evaluate the oncologic benefit, these data suggest a short course of AAT is considerably better tolerated than longer courses of AAT, with grade 3 toxicity rates similar to long courses of single-agent androgen deprivation therapy alone.