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

Ipilimumab plus nivolumab and DNA-repair defects in AR-V7-expressing metastatic prostate cancer. Oncotarget. 2018 Jun 19;9(47):28561-28571 Authors: Boudadi K, Suzman DL, Anagnostou V, Fu W, Luber B, Wang H, Niknafs N, White JR, Silberstein JL, Sullivan R, Dowling D, Harb R, Nirschl TR, Veeneman BA, Tomlins SA, Wang Y, Jendrisak A, Graf RP, Dittamore R, Carducci MA, Eisenberger MA, Haffner MC, Meeker AK, Eshleman JR, Luo J, Velculescu VE, Drake CG, Antonarakis ES 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...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research