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Current Cancer Therapy Reviews

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ISSN (Print): 1573-3947
ISSN (Online): 1875-6301

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Meta-Analysis

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

Author(s): Vinod Solipuram*, Harish Gopalakrishna, Gayatri Nair and Akhila Mohan

Volume 17, Issue 4, 2021

Published on: 16 June, 2021

Page: [255 - 260] Pages: 6

DOI: 10.2174/1573394717666210616152341

Price: $65

Abstract

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.

Keywords: Metastatic pancreatic cancer, pancreatic cancer, pancreatic adenocarcinoma, PEGPH20, Pegvorhyaluronidase alfa.

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Graphical Abstract

[1]
Cancer of the Pancreas - Cancer Stat Facts. SEER n.d. Available from: https://seer.cancer.gov/statfacts/html/pancreas.html
[2]
Pourshams A, Sepanlou SG, Ikuta KS, Bisignano C, Safiri S, Roshandel G. The global, regional, and national burden of pancreatic cancer and its attributable risk factors in 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol Hepatol 2019; 4(12): 934-47.
[http://dx.doi.org/10.1016/S2468-1253(19)30347-4] [PMID: 31648972]
[3]
Azar I, Virk G, Esfandiarifard S, Wazir A, Mehdi S. Treatment and survival rates of stage IV pancreatic cancer at VA hospitals: A nation-wide study. J Gastrointest Oncol 2019; 10(4): 703-11.
[http://dx.doi.org/10.21037/jgo.2018.07.08] [PMID: 31392051]
[4]
Kleeff J, Korc M, Apte M, et al. Pancreatic cancer. Nat Rev Dis Primers 2016; 2: 16022.
[http://dx.doi.org/10.1038/nrdp.2016.22] [PMID: 27158978]
[5]
Adamska A, Domenichini A, Falasca M. Pancreatic ductal adenocarcinoma: Current and evolving therapies. Int J Mol Sci 2017; 18(7): E1338.
[http://dx.doi.org/10.3390/ijms18071338] [PMID: 28640192]
[6]
Hajatdoost L, Sedaghat K, Walker EJ, Thomas J, Kosari S. Chemotherapy in pancreatic cancer: A systematic review. Medicina (Kaunas) 2018; 54(3): E48.
[http://dx.doi.org/10.3390/medicina54030048] [PMID: 30344279]
[7]
Coppola S, Carnevale I, Danen EHJ, et al. A mechanopharmacology approach to overcome chemoresistance in pancreatic cancer. Drug Resist Updat 2017; 31: 43-51.
[http://dx.doi.org/10.1016/j.drup.2017.07.001] [PMID: 28867243]
[8]
Kudo D, Suto A, Hakamada K. The development of a novel therapeutic strategy to target hyaluronan in the extracellular matrix of pancreatic ductal adenocarcinoma. Int J Mol Sci 2017; 18(3): E600.
[http://dx.doi.org/10.3390/ijms18030600] [PMID: 28282922]
[9]
Papakonstantinou E, Roth M, Karakiulakis G. Hyaluronic acid: A key molecule in skin aging. Dermatoendocrinol 2012; 4(3): 253-8.
[http://dx.doi.org/10.4161/derm.21923] [PMID: 23467280]
[10]
Hingorani SR, Zheng L, Bullock AJ, et al. HALO 202: Randomized phase II study of PEGPH20 plus nab-paclitaxel/gemcitabine versus nab-paclitaxel/gemcitabine in patients with untreated, metastatic pancreatic ductal adenocarcinoma. J Clin Oncol 2018; 36(4): 359-66.
[http://dx.doi.org/10.1200/JCO.2017.74.9564] [PMID: 29232172]
[11]
Hingorani SR, Harris WP, Beck JT, et al. Phase Ib study of PEGylated recombinant human hyaluronidase and gemcitabine in patients with advanced pancreatic cancer. Clin Cancer Res 2016; 22(12): 2848-54.
[http://dx.doi.org/10.1158/1078-0432.CCR-15-2010] [PMID: 26813359]
[12]
Kultti A, Zhao C, Singha NC, et al. Accumulation of extracellular hyaluronan by hyaluronan synthase 3 promotes tumor growth and modulates the pancreatic cancer microenvironment. BioMed Res Int 2014; 2014: 817613.
[http://dx.doi.org/10.1155/2014/817613] [PMID: 25147816]
[13]
Thompson CB, Shepard HM, O’Connor PM, et al. Enzymatic depletion of tumor hyaluronan induces antitumor responses in preclinical animal models. Mol Cancer Ther 2010; 9(11): 3052-64.
[http://dx.doi.org/10.1158/1535-7163.MCT-10-0470] [PMID: 20978165]
[14]
Higgins JPT, Altman DG, Gøtzsche PC, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 2011; 343: d5928.
[http://dx.doi.org/10.1136/bmj.d5928] [PMID: 22008217]
[15]
Shamseer L, Moher D, Clarke M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: Elaboration and explanation. BMJ 2015; 350: g7647.
[http://dx.doi.org/10.1136/bmj.g7647] [PMID: 25555855]
[16]
Berger VW, Alperson SY. A general framework for the evaluation of clinical trial quality. Rev Recent Clin Trials 2009; 4(2): 79-88.
[http://dx.doi.org/10.2174/157488709788186021] [PMID: 19463104]
[17]
GRADE handbook. Available from: https://gdt.gradepro.org/app/handbook/handbook.html
[18]
GRADEpro. Available from: https://gradepro.org/cite/
[19]
Chapter 10: Analysing data and undertaking meta-analyses. Available from: /handbook/current/chapter-10
[20]
Ramanathan RK, McDonough SL, Philip PA, et al. Phase IB/II randomized study of folfirinox plus pegylated recombinant human hyaluronidase versus FOLFIRINOX alone in patients with metastatic pancreatic adenocarcinoma: SWOG S1313. J Clin Oncol 2019; 37(13): 1062-9.
[http://dx.doi.org/10.1200/JCO.18.01295] [PMID: 30817250]
[21]
Van Cutsem E, Tempero MA, Sigal D, et al. Randomized phase III trial of pegvorhyaluronidase alfa with nab-paclitaxel plus gemcitabine for patients with hyaluronan-high metastatic pancreatic adenocarcinoma. J Clin Oncol 2020; 38(27): 3185-94.
[http://dx.doi.org/10.1200/JCO.20.00590] [PMID: 32706635]
[22]
Sohal DPS, Kennedy EB, Cinar P, et al. Metastatic pancreatic cancer: ASCO guideline update. J Clin Oncol 2020; 38: JCO2001364.
[http://dx.doi.org/10.1200/JCO.20.01364] [PMID: 32755482]
[23]
Wong KM, Horton KJ, Coveler AL, Hingorani SR, Harris WP. Targeting the tumor stroma: The biology and clinical development of Pegylated Recombinant Human Hyaluronidase (PEGPH20). Curr Oncol Rep 2017; 19(7): 47.
[http://dx.doi.org/10.1007/s11912-017-0608-3] [PMID: 28589527]
[24]
IPI-926-03. OLIVE Lab. Available from: https://www.OliveLab.org/ipi-926-03.html
[25]
Catenacci DVT, Junttila MR, Karrison T, et al. Randomized phase Ib/II study of gemcitabine plus placebo or vismodegib, a hedgehog pathway inhibitor, in patients with metastatic pancreatic cancer. J Clin Oncol 2015; 33(36): 4284-92.
[http://dx.doi.org/10.1200/JCO.2015.62.8719] [PMID: 26527777]

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