Abstract
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.
Highlights
Despite recent advances in our understanding of this disease, pancreatic adenocarcinoma remains one of the deadliest cancers, with a five-year survival rate of 8% [1]
An additional five articles were found through crosstherapies in pancreatic adenocarcinoma [11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107]
Despite numerous clinical trials with varying treatment combinations and dosages, this meta-analysis demonstrates no clinical benefit of any vascular endothelial growth factor (VEGF) or vascular endothelial growth factor receptor (VEGFR)-targeted treatment: Neither bevacizumab, sorafenib, axitinib, or aflibercept increased the overall survival compared to controls
Summary
Despite recent advances in our understanding of this disease, pancreatic adenocarcinoma remains one of the deadliest cancers, with a five-year survival rate of 8% [1]. For patients with a good physical condition, treatment with FOLFIRINOX,2consisting of 5-FU, oxaliplatin, and irinotecan, increased survival to 11.1 months compared to gemcitabine alone, 0.72, 95% confidence interval (CI), 0.62 to 0.83) [3,4]. For patients with a good physical condition, but this treatment comes at the cost of potentially severe side-effects [5]. Based on recent advances in our understanding of the biology of pancreatic cancer, novel. 11.1 months compared to gemcitabine alone, but this treatment comes at the cost of potentially severe therapeutic strategies side-effects [5]. The dense stroma is a characteristic of many solid butadvances in particular of understanding pancreatic cancer [6].biology
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