(UroToday.com) Localized high-risk prostate cancer (LHRPC) is associated with a substantial risk of disease recurrence and prostate-cancer specific mortality. Multiple groups have focused on testing androgen-signaling axis inhibitors in the neoadjuvant setting for LHRPC to identify patients that may benefit long-term from such interventions. This more intensive androgen axis inhibition has resulted in a subset of patients having a pathologic complete response (pCR) and longer-term recurrence-free survival. Tumors resistant to neoadjuvant androgen axis inhibition tend to have certain molecular characteristics such as the presence of the androgen receptor (AR) splice variant AR-V7, loss of PTEN expression, and increased expression of the glucocorticoid receptor (GR).
To further evaluate intensive neoadjuvant androgen-axis inhibitors, Dr. Efstathiou and colleagues pursued the following study:
Pre-and post-treatment tissue was captured and analyzed for morphologic and molecular features that may be correlated with response.
In total, 81 patients consented to this study. The consort diagram is shown below:
Patient characteristics in each arm are shown below.
Treatment discontinuation due to adverse events were comparable between arms, and there were no grade 5 adverse events or new safety concerns with combined abiraterone and apalutamide therapy. In Arm A, 2 patients required dose reduction and 6 patients required dose reduction in the combined arm.
As with prior neoadjuvant studies, responses to therapy were variable. In this study, ~40% of patients had organ-confined disease at the time of prostatectomy, and pCR rates were 16% in the apalutamide arm (Arm A) versus 10% in the apalutamide + abiraterone acetate Arm B.
In a multivariate analysis for association between clinicopathologic and molecular findings and response, loss of PTEN, presence of AR-V7, and clinical stage were associated with higher tumor volume after neoadjuvant therapy at the time of surgery.
The authors then looked to develop candidate molecular signatures that may be able to predict response to neoadjuvant therapy. The presence of any 1 of PTEN loss, ARV-7, high expression of GR, or high Ki-67 in a pre-treatment specimen was significantly predictive of lack of response to neoadjuvant therapy. To increase sensitivity, the authors removed PTEN loss from the signature and found that the lack of GR expression, low Ki-67 expression, and lack of ARV-7 predicted 84% of pCRs.
In summary, the authors concluded that intensive androgen-axis inhibition is safe for 6 months prior to surgery in LHRPC. Therapy response is variable, but the molecular characterization of pre-treatment samples may predict which patients are more likely to respond.
Presented by: Eleni Efstathiou, MD, PhD, Associate Professor, Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
Written by: Alok Tewari, MD, Ph.D., Medical Oncology Fellow at the Dana-Farber Cancer Institute, at the 2020 American Society of Clinical Oncology Virtual Annual Meeting (#ASCO20), May 29th-May 31st, 2020