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Poster display session

2060 - Musculoskeletal Events (MSEs) with PEGPH20 Treatment and Management in Patients with Previously Untreated Metastatic Pancreatic Ductal Adenocarcinoma (mPDA)

Date

09 Sep 2017

Session

Poster display session

Presenters

Andrea Bullock

Citation

Annals of Oncology (2017) 28 (suppl_5): v209-v268. 10.1093/annonc/mdx369

Authors

A. Bullock1, P. Vervaet2, W. Wu3, D. Chondros2, S.R. Hingorani4, A. Hendifar5

Author affiliations

  • 1 Hematol/oncol, Beth Israel Deaconess Medical Center, 02215 - Boston/US
  • 2 Clinical, Halozyme Therapeutics, 92121 - San Diego/US
  • 3 Biostats, Halozyme Therapeutics, 92121 - San Diego/US
  • 4 Oncology, Fred Hutchinson Cancer Research Center, 98109 - Seattle, WA/US
  • 5 Cedars-sinai Medical Center, Samuel Oschin Cancer Center, 90048 - Los Angeles/US
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Resources

Abstract 2060

Background

Hyaluronan (HA) accumulation in the tumor microenvironment is associated with poor outcomes. PEGylated recombinant human hyaluronidase PH20 (PEGPH20) degrades HA, facilitating access of cancer therapies. MSEs (e.g., muscle spasms, arthralgia, and myalgia) occur frequently with PEGPH20, and were dose-limiting in Phase 1 studies. Here we describe MSEs observed in a phase 2 study of PEGPH20 (P) plus gemcitabine/nab-paclitaxel (AG) vs AG in patients with previously untreated mPDA.

Methods

In Stage 1 of the study, patients were randomized 1:1 to PAG or AG (P 3 µg/kg IV 2x/wk x 3 wks in Cycle 1, then once weekly x 3 wks in Cycle 2+) every 28 days. A clinical hold due to an imbalance in thromboembolic events resulted in ∼40% of patients discontinuing PEGPH20. After the clinical hold, patients were randomized 2:1 to PAG vs AG (Stage 2). Dexamethasone 8 mg was administered orally within 2 hours before and 8-12 hours after PEGPH20 to lessen the severity of MSEs. We analyzed adverse event frequency, severity, timing, and management.

Results

279 patients were enrolled; 260 patients comprise the safety population. All patients received a median of 3.3 months of study treatment. The proportion of patients with treatment-emergent MSEs was higher in the PAG arm vs AG arm (all grade, 86% vs 46%; grade 3, 19% vs 6%). Grade 4/5 MSEs were not observed. The most common MSEs (all grade/grade 3, PAG vs AG) were muscle spasms in lower and upper extremities (58%/13% vs. 6%/1%), arthralgia (28%/2% vs.14%/1%) and myalgia (27%/5% vs.12%/0). Median (range) time to MSE onset was 2 (0-287) days for PAG and 8 (0-196) days for AG. Median duration of Grade 3 MSEs was 9 (5-14) days for PAG vs 8.5 (2-22) days for AG. Five (4%) patients experienced MSEs that led to PAG discontinuation: muscle spasms (n = 4) and myalgia (n = 1). Medications were administered in 57% (PAG) vs. 20% (AG) of MSE episodes, predominantly to manage Grade 3 MSEs.

Conclusions

MSEs are commonly observed with AG treatment, and even more frequently with PAG. MSEs are primarily mild (Grade 1/2) and infrequently lead to treatment discontinuation. The time course, associated dose modifications, and management of MSEs will be presented.

Clinical trial identification

NCT01839487

Legal entity responsible for the study

Halozyme Therapeutics, Inc.

Funding

Halozyme Therapeutics, Inc.

Disclosure

A. Bullock: Consulting or advisory board participation support: Halozyme, Celgene, and EMD Serono. P. Vervaet, W. Wu, D. Chondros: Employee of Halozyme Therapeutics. S.R. Hingorani: Consulting or Advisory Role: Halozyme, Aduro Biotech Research Funding: Halozyme (institution). A. Hendifar: Consulting or Advisory Role: Genentech, Novartis, Ipsen, Perthera Travel, Accommodations, Expenses: Halozyme.

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