PEGPH20 Plus mFOLFIRINOX Worsens OS Among Patients With Pancreatic Cancer

Adding pegylated recombinant human hyaluronidase (PEGPH20) to modified FOLFIRINOX (mFOLFIRINOX) may negative affect overall survival (OS) among patients with pancreatic cancer, according to research being presented at the 2018 Gastrointestinal Cancers Symposium in San Francisco, California.¹

Preclinical models suggested that PEGPH20, which degrades hyaluronan, would improve OS among patients with metastatic pancreatic adenocarcinoma. For this randomized phase 1b/2 study (ClinicalTrials.gov Identifier: NCT01959139), researchers evaluated the safety and efficacy of PEGPH20 with mFOLFIRINOX vs mFOLFIRINOX alone among 138 patients with good performance status and adequate organ function.

Random assignment was 1:1. Patients assigned to PEGPH20 received prophylaxis for thromboembolic (TE) events.

The study closed to accrual after a futility analysis showed a hazard ratio for OS of 0.44 in favor of mFOLFIRINOX. After a follow-up of more than 2 years, the estimated median OS was 7.6 months with PEGPH20 vs 15.1 months with mFOLFIRINOX.

Toxicity was, furthermore, worse in the PEGPH20 arm, with higher rates of grade 3 to 4 diarrhea, fatigue, nausea, and vomiting. Even with prophylaxis, 9% of patients had a TE event in the PEGPH20 arm vs 5% with mFOLFIRINOX only.

The authors concluded that adding “PEGPH20 to [mFOLFIRINOX] is not recommended for further study and appears to be detrimental.”

Read more of Cancer Therapy Advisor‘s coverage of the 2018 Gastrointestinal Cancers Symposium by visiting the conference page.

Reference

1. Ramanathan RK, McDonough S, Philip PA, et al. A phase IB/II randomized study of mFOLFIRINOX (mFFOX) + pegylated recombinant human hyaluronidase (PEGPH20) versus mFFOX alone in patients with good performance status metastatic pancreatic adenocarcinoma (mPC): SWOG S1313 (NCT #01959139). Oral presentation at: 2018 Gastrointestinal Cancers Symposium; January 18-20, 2018; San Francisco, CA.