The glycosaminoglycan hyaluronan (HA) is a major component of the extracellular matrix (ECM). Data from a recent phase II trial suggest that 25-36% of tumours from stage IV previously untreated pancreatic cancer patients have high levels of HA . It is thought that HA can act as a barrier preventing drug penetrance. Hyaluronidase is an enzyme that degrades HA and preliminary data suggests that a systemically delivered formulation of the enzyme can increase overall survival time of late stage pancreatic cancer patients expressing high levels of HA (HAhigh) when combined with nab-paclitaxel and gemcitabine compared with nab-paclitaxel and gemcitabine alone .
It is important to note that due to unavoidable low patient numbers this is only a trend, however subsequent phase III clinical trials will confirm or refute the trend. Increased progression-free survival of HAhigh patients was statistically significant. The stratification of HA status was performed retrospectively and suggests that for future trials eligibility should be determined based on HA status. This is an important strategy that is relevant to all pancreatic cancer therapeutics in development. In the era of next generation sequencing it is important to gather as much patient tumour data as possible with the goal of uncovering biomarkers of efficaciousness which can be used to select patients for future clinical trials.
The importance of HA status necessitated the development of a companion diagnostic. Hyaluronidase can potentially increase drug penetrance and efficaciousness in a subset of pancreatic cancer patients.
- ‘High Response Rate and PFS with PEGPH20 Added to Nab-Paclitaxel/gemcitabine in Stage IV Previously Untreated Pancreatic Cancer Patients with High-HA Tumors: Interim Results of a Randomized Phase II Study.’ Accessed 17 March 2016. http://meetinglibrary.asco.org/print/1991286.
- ‘Halozyme Phase 2 Clinical Study Of Investigational Drug PEGPH20 Shows Doubling Of Progression-Free Survival And Improvement Trend In Overall Survival In High HA Metastatic Pancreatic Cancer Patients’. Accessed 17 March 2016. http://www.streetinsider.com/Press+Releases/Halozyme+Phase+2+Clinical+Study+Of+Investigational+Drug+PEGPH20+Shows+Doubling+Of+Progression-free+Survival+And+Improvement+Trend+In+Overall+Survival+In+High+HA+Metastatic+Pancreatic+Cancer+Patients/10609719.html.