Some notable inclusion criteria include adult men with adenocarcinoma of the prostate without neuroendocrine or small cell features, prostate-specific antigen (PSA) doubling time of <= 10 months, castrate levels of testosterone, at least a 4-week washout period following treatment with first generation anti-androgen therapy (e.g. bicalutamide), at least a 5-week washout period after 5-alpha reductase inhibitors or estrogens, at least 4 weeks from major surgery or radiation therapy, and ECOG 0 or 1. Notable exclusion criteria include confirmed distant metastases, prior treatment with second-generation anti-androgens, prior chemotherapy, and various existing medical conditions including other malignancies and heart disease.
Eligible patients were randomized 2:1 to APA + ADT or PBO + ADT. Patients who developed distant metastases were eligible for subsequent therapy including with abiraterone + prednisone. Oncologic outcomes and incidence of treatment-emergent adverse events (TEAEs) were evaluated.
The primary outcome measure of the trial is metastasis-free survival (MFS) defined from the time of randomization to the first bone or soft tissue metastasis on bone scan, CT or MRI scan performed throughout the study, or death due to any cause. Secondary outcomes are time to metastasis, progression-free survival (PFS), time to symptomatic progression, overall survival, and time to initiation of cytotoxic chemotherapy.
Prior analysis showed an improved MFS and symptomatic progression. The updated 1-year analysis continued to show a benefit in PFS (HR 0.5 95% CI 0.39-0.63) for the APA cohort with a median treatment duration of 25.7 months. There were significantly lower rates of treatment discontinuation due to progressive disease and adverse events in the APA cohort 27% and 13% versus 73% and 8% in the PBO cohort. There was no significant change in TEAEs at the 1-year update. TEAEs included rash in 5.2 %, falls in 2.4%, fractures in 3.1%; there were no grade 4 or 5 events.
In conclusion, apalutamide plus ADT results in improvement in MFS and symptomatic progression in men with nmCRPC. An updated 1-year analysis revealed continued improvement in PFS and no increase in treatment-related adverse events.
Presented by: Eric Jay Small MD, FASCO, deputy director of UCSF Helen Diller Family Comprehensive Cancer Center, chief of the Division of Hematology and Oncology in the Department of Medicine at the University of California, San Francisco, and professor in residence in the Department of Medicine and Department of Urology.
Written by: Selma Masic, MD, Urologic Oncology Fellow (SUO), Fox Chase Cancer Center, Philadelphia, PA. Twitter:@selmasic at the 2019 American Society of Clinical Oncology Genitourinary Cancers Symposium, (ASCO GU) #GU19, February 14-16, 2019 - San Francisco, CA