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Clinical Trials Targeting the Stroma in Pancreatic Cancer: A Systematic Review and Meta-Analysis

1
Laboratory of Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105AZ Amsterdam, The Netherlands
2
Department of Medical Oncology, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Meibergdreef 9, 1105AZ Amsterdam, The Netherlands
3
Medical Library, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105AZ Amsterdam, The Netherlands
4
Cochrane Netherlands, Julius Center, University Medical Center Utrecht, Utrecht University, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
5
Department of Surgery, Erasmus MC, Dr. Molewaterplein 40, 3015GD Rotterdam, The Netherlands
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(5), 588; https://doi.org/10.3390/cancers11050588
Received: 21 March 2019 / Revised: 19 April 2019 / Accepted: 22 April 2019 / Published: 26 April 2019
(This article belongs to the Special Issue Advances in Pancreatic Cancer Research)
The tumor microenvironment plays an important role in the initiation and progression of pancreatic adenocarcinoma (PDAC). In this systematic review, we provide an overview of clinical trials with stroma-targeting agents. We systematically searched MEDLINE/PubMed and the EMBASE database, using the PRISMA guidelines, for eligible clinical trials. In total, 2330 records were screened, from which we have included 106 articles. A meta-analysis could be performed on 51 articles which describe the targeting of the vascular endothelial growth factor (VEGF) pathway, and three articles which describe the targeting of hyaluronic acid. Anti-VEGF therapies did not show an increase in median overall survival (OS) with combined hazard ratios (HRs) of 1.01 (95% confidence interval (CI) 0.90–1.13). Treatment with hyaluronidase PEGPH20 showed promising results, but, thus far, only in combination with gemcitabine and nab-paclitaxel in selected patients with hyaluronic acid (HA)high tumors: An increase in median progression free survival (PFS) of 2.9 months, as well as a HR of 0.51 (95% CI 0.26–1.00). In conclusion, we found that anti-angiogenic therapies did not show an increased benefit in median OS or PFS in contrast to promising results with anti-hyaluronic acid treatment in combination with gemcitabine and nab-paclitaxel. The PEGPH20 clinical trials used patient selection to determine eligibility based on tumor biology, which underlines the importance to personalize treatment for pancreatic cancer patients. View Full-Text
Keywords: PDAC; stroma; clinical trial; systematic review; targeted therapy PDAC; stroma; clinical trial; systematic review; targeted therapy
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van Mackelenbergh, M.G.; Stroes, C.I.; Spijker, R.; van Eijck, C.H.; Wilmink, J.W.; Bijlsma, M.F.; van Laarhoven, H.W. Clinical Trials Targeting the Stroma in Pancreatic Cancer: A Systematic Review and Meta-Analysis. Cancers 2019, 11, 588.

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