Current Status of Monoclonal Antibodies-Based Therapies in Castration-Resistant Prostate Cancer: A Systematic Review and Meta-Analysis of Clinical Trials

Abstract

BackgroundMultiple patients with prostate cancer become resistant to castration therapies, which is termed castrationresistant prostate cancer (CRPC). PurposeThe purpose of this review is to assess the status of efficacy (≥50% decline in prostate-specific antigen (PSA), progression-free survival (PFS), and overall survival (OS)) and safety (grade 3-4 adverse effects) of monoclonal antibodies in CRPC. Data sourceWe searched databases including PubMed, Embase, Cochrane, Web of Science, and ClinicalTrials.gov. ResultsHazard ratios of PFS and OS were 0.77 (95% CI = 0.69-0.87, I 2 = 53%) and 0.98 (95% CI = 0.86-1.11, I 2 = 40%), respectively, in the favor of monoclonal antibodies as compared to placebo. Risk ratio (RR) of >50% decline in PSA was 1.99 (95% CI = 0.97-4.08, I 2 = 53%) in favor of monoclonal antibodies. Pooled incidence of >50% decline in PSA levels was 15% (95% CI = 0.1-0.23, I 2 = 83%), 29% (95% CI = 0.14-0.51, I 2 = 93%), 63% (95% CI = 0.49-0.76, I 2 = 77%), and 88% (95% CI = 0.81-0.93, I 2 = 0%) in single, two, three, and four-drug regimens, respectively. ConclusionMonoclonal antibodies are well tolerated and showed better PFS as compared to placebo. However, OS was only improved with ipilimumab. Denosumab delayed skeletal-related adverse events as compared to zoledronic acid. More multicenter double-blind clinical trials may be needed to confirm these results.

The Immunotherapy and Immunosuppressive Signaling in Therapy-Resistant Prostate Cancer

“…Ipilimumab, a popular inhibitor of the immune checkpoint molecule CTLA-4, was used to treat in prostate cancer patients after it was approved by the FDA to treat melanoma. Ipilimumab, when taken as a monotherapy or combination treatment in phase I/II clinical trials of mCRPC, did not exacerbate immune-related adverse effects [ 57 ]. The combination of ipilimumab and radiotherapy improved OS (2- to 3-fold higher) in patients with mCRPC after docetaxel, while combination therapy with the PD-1 inhibitor nivolumab showed only modest activity in AR-V7-positive mCRPC patients [ 41 ].…”