Efficacy and Safety of PEGPH20 in Pancreatic Cancer: Systematic Review and Meta-analysis

Introduction: Pancreatic cancer is an aggressive tumor, and an estimated 57,600 new cases and 47,050 deaths were reported in 2020 in the US alone. Recent studies have targeted the tumor microenvironment (TME) for better delivery of systemic chemotherapy, like PEGPH20, which degrades hyaluronic acid in the extracellular matrix (ECM). A meta-analysis of these Randomized controlled trials (RCTs) to test the efficacy of PEGPH20 was performed. Methods: A systematic search was performed using PubMed, Embase, and Cochrane library without language limitations from inception to July 30, 2020. A total of 59 articles were identified, and 3 RCTs were included in the final analysis. The primary outcome was progression-free survival (PFS), and secondary outcomes were overall survival (OS), deaths from adverse events, thromboembolic events, serious adverse events (SAE), and febrile neutropenia. Results: There was no statistically significant improvement in PFS (HR= 0.94; 95%CI (0.79, 1.11)) in the PEGPH20 group when compared to the standard treatment/placebo group. There was no significant difference among OS (HR= 0.99, 95%CI (0.83, 1.17), deaths from adverse events (RR= 0.97; 95%CI (0.54, 1.73)), thromboembolic events (RR= 1.49; 95%CI (0.92, 2.44)), and febrile neutropenia (RR= 0.88; 95%CI (0.45, 1.72), but a statistically significant increase in SAE (RR = 1.59; 95%CI (1.01, 2.52) in the PEGPH20 group compared to the placebo group was observed. Conclusion: This meta-analysis showed that PEGPH20 did not improve the PFS or OS. Moreover, there was an increased incidence of serious adverse events using PEGPH20 compared to standard therapies.