Ipilimumab plus nivolumab and DNA-repair defects in AR-V7-expressing metastatic prostate cancer.

TitleIpilimumab plus nivolumab and DNA-repair defects in AR-V7-expressing metastatic prostate cancer.
Publication TypeJournal Article
Year of Publication2018
JournalOncotarget
Volume9
Issue47
Pagination28561-28571
Date Published2018
Abstract

AR-V7-expressing metastatic prostate cancer is an aggressive phenotype with poor progression-free survival (PFS) and overall survival (OS). Preliminary evidence suggests that AR-V7-positive tumors may be enriched for DNA-repair defects, perhaps rendering them more sensitive to immune-checkpoint blockade. We enrolled 15 metastatic prostate cancer patients with AR-V7-expressing circulating tumor cells into a prospective phase-2 trial. Patients received nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for four doses, then maintenance nivolumab 3 mg/kg every 2 weeks. Targeted next-generation sequencing was performed to determine DNA-repair deficiency (DRD) status. Outcomes included PSA response rates, objective response rates (ORR), PSA progression-free survival (PSA-PFS), clinical/radiographic PFS and OS. Median age of participants was 65, median PSA was 115 ng/mL, 67% had visceral metastases, and 60% had ≥4 prior systemic therapies. Six of 15 men (40%) had DRD mutations (three in , two in , one in ; none had microsatellite instability). Overall, the PSA response rate was 2/15 (13%), ORR was 2/8 (25%) in those with measurable disease, median PSA-PFS was 3.0 (95%CI 2.1-NR) months, PFS was 3.7 (95%CI 2.8-7.5) months, and OS was 8.2 (95%CI 5.5-10.4) months. Outcomes appeared generally better in DRD+ vs. DRD- tumors with respect to PSA responses (33% vs. 0%; =0.14, nonsignificant), ORR (40% vs. 0%; =0.46, nonsignificant), PSA-PFS (HR 0.19; <0.01, significant), PFS (HR 0.31; =0.01, significant), and OS (HR 0.41; =0.11, nonsignificant). There were no new safety concerns. Ipilimumab plus nivolumab demonstrated encouraging efficacy in AR-V7-positive prostate cancers with DRD mutations, but not in the overall study population.

URLhttp://www.impactjournals.com/oncotarget/misc/linkedout.php?pii=25564
DOI10.18632/oncotarget.25564
Short TitleOncotarget
X
Enter your linkblue username.
Enter your linkblue password.
Secure Login

This login is SSL protected

Loading