Efficacy and Toxicity of Anti-VEGF Agents in Patients with Castration-Resistant Prostate Cancer: a Meta-analysis of Prospective Clinical Studies

Background: Blocking angiogenesis by targeting vascular endothelial growth factor (VEGF) signalingpathway to inhibit tumor growth has proven to be successful in treating a variety of different metastatic tumortypes, including kidney, colon, ovarian, and lung cancers, but its role in castration-resistant prostate cancer(CRPC) is still unknown. We here aimed to determine the efficacy and toxicities of anti-VEGF agents in patientswith CRPC. Materials and
Methods: The databases of PubMed, Web of Science and abstracts presented at theAmerican Society of Clinical Oncology up to March 31, 2014 were searched for relevant articles. Pooled estimatesof the objective response rate (ORR) and prostate-specific antigen (PSA) response rate (decline ≥50%) werecalculated using the Comprehensive Meta-Analysis (version 2.2.064) software. Median weighted progressionfreesurvival (PFS) and overall survival (OS) time for anti-VEGF monotherapy and anti-VEGF-based doubletswere compared by two-sided Student’s t test.
Results: A total of 3,841 patients from 19 prospective studies (4randomized controlled trials and 15 prospective nonrandomized cohort studies) were included for analysis.The pooled ORR was 12.4% with a higher response rate of 26.4% (95%CI, 13.6-44.9%) for anti-VEGF-basedcombinations vs. 6.7% (95%CI, 3.5-12.7%) for anti-VEGF alone (p=0.004). Similarly, the pooled PSA response ratewas 32.4% with a higher PSA response rate of 52.8% (95%CI: 40.2-65.1%) for anti-VEGF-based combinationsvs. 7.3% (95%CI, 3.6-14.2%) for anti-VEGF alone (p<0.001). Median PFS and OS were 6.9 and 22.1 months withweighted median PFS of 5.6 vs. 6.9 months (p<0.001) and weighted median OS of 13.1 vs. 22.1 months (p<0.001)for anti-VEGF monotherapy vs. anti-VEGF-based doublets.
Conclusions: With available evidence, this pooledanalysis indicates that anti-VEGF monotherapy has a modest effect in patients with CRPC, and clinical benefitsgained from anti-VEGF-based doublets appear greater than anti-VEGF monotherapy.