Ramanathan RK, et al. - In this phase 2 open-label study, researchers assessed overall survival (OS) among patients with untreated metastatic pancreatic cancer (mPC), a performance status of 0 to 1, and adequate organ function following randomization (1:1) to pegylated recombinant human hyaluronidase (PEGPH20) plus mFOLFIRINOX (modified fluorouracil, leucovorin, irinotecan, and oxaliplatin) or to mFOLFIRINOX alone (n = 138). Compared to twice-weekly dosages of PEGPH20 used in the phase I study, 3 µg/kg every 2 weeks were more tolerable and so were used in this phase 2 study. In patients unselected for tumor hyaluronan (HA) status, a detrimental impact of PEGPH20 added to mFOLFIRINOX was observed. Compared with mFOLFIRINOX alone, PEGPH20 plus mFOLFIRINOX was associated with increased toxicity (mostly GI and thromboembolic events) and decreased treatment duration. In the mFOLFIRINOX arm vs in the PEGPH20 combination arm, the estimated median OS was 14.4 months vs 7.7 months, respectively. This was the longest median OS reported to date in the mFOLFIRINOX control arm and can be considered for patients with good PS.