Top Line: Tumor microenvironment plays a particularly important role in pancreatic adenocarcinoma, as these tumors are often surrounded by a dense fibrous stroma.
The Study: A major constituent of that stroma is hyaluronan (aka hyaluronaic acid aka your friendly neighborhood anti-wrinkle dermal filler). Pegvorhyaluronidase alpha (PEGPH20) is a recombinant hyaluronidase that degrades tumor hyaluronan. While it may have anti-tumor activity, its main potential benefit is increased chemotherapy penetration into the dense tumor stroma. HALO-301 was a phase 3 trial where patients with untreated, metastatic pancreatic cancer were randomized to receive nab-paclitaxel and gemcitabine with or without PEGPH20. There are a couple of key points here. First, the tumor had to be “hyaluronan-high,” which means 50% or more of the extracellular matrix had to stain for hyaluronan. Second, there was concern for increased thromboembolic events in the phase 2 trial, so prophylactic enoxaparin was self-administered in both arms. Unfortunately, there was no improvement with PEGPH20 in median overall survival (just over 11 months either way) or median progression-free survival (just over 7 months). However, grade 3+ sepsis and bleeding were higher with PEGPH20 than with placebo.
TBL: While we appreciate the out-of-the-box concept, targeting the tumor stroma with PEGPH20 does not improve clinical outcomes for patients receiving gem/abraxane for metastatic pancreatic cancer. | Cutsem, J Clin Oncol 2020