ASCO GU 2019: Pembrolizumab in Men With Heavily Treated Metastatic Castration-Resistant Prostate Cancer

San Francisco, CA (UroToday.com) Immune checkpoint inhibition for prostate cancer has been met with significant challenges in the immunotherapy era. Unlike the dramatic and responses seen in melanoma, lung, kidney, and bladder cancer, prostate cancer has not had the same success in unselected patients. Even in patients with MSI high (microsatellite instability) disease, 7/11 patients did not have an objective response and 5/6 did not have a PSA50 (decline in PSA by 50%)1. This study evaluates the off-label use of pembrolizumab in a heavily pre-treated population of patients with mCRPC.

This is a single center retrospective study of 51 men who received one or more cycles of off-label pembrolizumab for mCRPC. The primary objective of this analysis was to describe the efficacy of pembrolizumab with respect to objective response, PSA response, time to treatment discontinuation, radiographic response, and overall survival. The secondary objectives were to describe the specific genomic results of all patients who received FoundationOne testing including the microsatellite instability status.
XUroToday ASCOGU2019 Matthew Tucker MD 1
Somatic tumor sequencing via FoundationOne was available in 18/51 men (35%). TMPRSS2-ERG fusion (12%), PTEN loss (10%), and AR amplification (8%) were the most frequent gene variants. Of the four patients with confirmed >90% PSA reductions, two of the four patients had an LRP1b.
UroToday ASCOGU2019 Matthew Tucker MD 1
In terms of baseline characteristics, this was a heavily pretreated population – 86% of patients had 3 or more prior lines of therapy. Most patients had previously received abiraterone (88%), docetaxel (86%), enzalutamide (80%), and sipuleucel-T (74%). The authors found that 16% of patients (8/51) had a >50% confirmed PSA decline with pembrolizumab, with 8% (4/51) having >90% PSA decline. Fifty-nine percent (30/51) of men were treated with some form of concurrent therapy along with pembrolizumab, most commonly enzalutamide (47%, 24/51).
UroToday ASCOGU2019 Matthew Tucker MD 1

Single agent pembrolizumab is an active treatment in a small proportion of patients with mCRPC. However, selection of these patients is challenging and we need predictive biomarkers because the vast majority of patients will not respond to single agent immunotherapy. Abstracts presented during this GU ASCO prospectively explore combination strategies (Ipi/Nivo, Pembro/Olaparib) which may improve the objective response rates for patients with mCRPC.

Presented by: Matthew Tucker, MD, Internal Medicine Doctor, Duke Health

Written By: Jason Zhu, MD. Fellow, Division of Hematology and Oncology, Duke University, Twitter: @TheRealJasonZhu at the 2019 American Society of Clinical Oncology Genitourinary Cancers Symposium, (ASCO GU) #GU19, February 14-16, 2019 - San Francisco, CA

References:
  1. Abida W, Cheng ML, Armenia J, et al. Microsatellite instability in prostate cancer and response to immune checkpoint blockade. American Society of Clinical Oncology; 2018.
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