Randomized Phase III trial of Pegvorhyaluronidase Alfa with nab-paclitaxel plus gemcitabine for patients with hyaluronan-high metastatic pancreatic adenocarcinoma
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PURPOSE: To evaluate the efficacy and safety of pegvorhyaluronidase alfa (PEGPH20) plus nab-paclitaxel/gemcitabine (AG) in patients with hyaluronan-high metastatic pancreatic ductal adenocarcinoma (PDA). PATIENTS AND METHODS: HALO 109-301 was a phase III, randomized, double-blind, placebo-controlled study. Patients ≥ 18 years of age with untreated, metastatic, hyaluronan-high PDA were randomly assigned 2:1 to PEGPH20 plus AG or placebo plus AG. Treatment was administered intravenously in 4-week cycles (3 weeks on, 1 week off) until progression or intolerable adverse events: PEGPH20 3.0 µg/kg twice per week for cycle 1 and once per week thereafter; nab-paclitaxel 125 mg/m 2 once per week; and gemcitabine 1,000 mg/m 2 once per week. The primary end point was overall survival (OS); secondary end points included progression-free survival (PFS), objective response rate (ORR), and safety. Response was independently assessed per RECIST v1.1. RESULTS: At data cutoff, 494 patients were randomly assigned, with 492 (327 for PEGPH20 and 165 for placebo) included in intention-to-treat analyses. Baseline characteristics were balanced for PEGPH20 plus AG versus placebo plus AG. There were 330 deaths, with a median OS of 11.2 months for PEGPH20 plus AG versus 11.5 months for placebo plus AG (hazard ratio [HR], 1.00; 95% CI, 0.80 to 1.27; P = .97); median PFS was 7.1 months versus 7.1 months (HR, 0.97 [95% CI, 0.75 to 1.26]); ORR was 47% versus 36% (ORR ratio, 1.29 [95% CI, 1.03 to 1.63]). Grade ≥ 3 adverse events with a ≥ 2% higher rate with PEGPH20 plus AG than with placebo plus AG included fatigue (16.0% v 9.6%), muscle spasms (6.5% v 0.6%), and hyponatremia (8.0% v 3.8%). CONCLUSION: The addition of PEGPH20 to AG increased the ORR but did not improve OS or PFS. The safety profile of PEGPH20 plus AG was consistent with that found in previous studies. These results do not support additional development of PEGPH20 in metastatic PDA.
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Randomized clinical trials combining PEG-hyaluronidase with standard-of-care chemotherapy for advanced PDAC did not increase overall survival, regardless of chemotherapy backbone or selection of patients with high hyaluronic acid by immunostaining.
“randomized clinical trials combining a pegylated hyaluronic acid degrading enzyme, PEG-hyaluronidase, with standard-of-care chemotherapy for advanced PDAC did not show an increase in overall survival regardless of chemotherapy backbone or selection of patients with high levels of hyaluronic acid by immunostaining172,173”
From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [172]
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References 42 · Cited by 499
- Authors
- Van Cutsem, E., Tempero, M. A., Sigal, D., Oh, D.-Y., Fazio, N., Macarulla, T., Hitre, E., Hammel, P., Hendifar, A. E., Bates, S. E., Li, C.-P., Hingorani, S. R., de la Fouchardiere, C., Kasi, A., Heinemann, V., Maraveyas, A., Bahary, N., Layos, L., Sahai, V., Zheng, L., Lacy, J., Park, J. O., Portales, F., Oberstein, P., Wu, W., Chondros, D., Bullock, A. J., & on behalf of the HALO 109-301 Investigators
- Affiliations
- Digestive Oncology, University Hospitals Gasthuisberg Leuven and KU Leuven, Leuven, Belgium
- University of California San Francisco Medical Center (US)
- Scripps Clinic (US)
- Seoul National University (KR)
- European Institute of Oncology (IT)
- Vall d'Hebron Hospital Universitari (ES)
- National Institute of Oncology (HU)
- Université Paris Cité (FR)
- Cedars-Sinai Medical Center (US)
- Columbia University Irving Medical Center (US)
- Taipei Veterans General Hospital (TW)
- University of Washington (US)
- Department of Medical Oncology, Centre Léon Bérard, Lyon, France
- University of Kansas Medical Center (US)
- LMU Klinikum (DE)
- Castle Hill Hospital (GB)
- University of Pittsburgh Medical Center (US)
- Institut Català d'Oncologia (ES)
- University of Michigan (US)
- Johns Hopkins University (US)
- Yale University (US)
- Samsung Medical Center (KR)
- Institut Regional du Cancer de Montpellier (FR)
- NYU Langone Health (US)
- Halozyme Therapeutics (United States) (US)
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Tempero, Margaret A.
- ORCID
- Tempero, Margaret A.
- Sigal, Darren
- Oh, Do-Youn
- Fazio, Nicola
- Macarulla, Teresa
- Hammel, Pascal
- Hendifar, Andrew E.
- Bates, Susan E.
- Li, Chung-Pin
- Hingorani, Sunil R.
- Kasi, Anup
- Heinemann, Volker
- Maraveyas, Anthony
- Bahary, Nathan
- Layos, Laura
- Sahai, Vaibhav
- Zheng, Lei
- Lacy, Jill
- Park, Joon Oh
- Portales, Fabienne
- Oberstein, Paul
- Bullock, Andrea J.
- Venue
- Journal of Clinical Oncology
- Published
- 2020-09-20
- Volume
- 38
- Issue
- 27
- Pages
- 3185-3194
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- PMC
- PMC7499614
- OpenAlex
- W3044807317
- Cited by
- 499
- References
- 42
- Citations by year
- 2026: 108 · 2025: 69 · 2024: 67 · 2023: 70 · 2022: 85 · 2021: 82 · 2020: 17
- FWCI
- 22.94
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Journal of Clinical Oncology (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Lirias (KU Leuven) (submittedVersion, other-oa)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc-nd)
- Seoul National University Open Repository (Seoul National University) (submittedVersion)
- Funders
- AstraZeneca
- Sanofi
- Celgene
- Servier
- Ipsen
- National Institutes of Health (UL1TR001863)
- Genentech
- National Cancer Institute (P50CA062924)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
- Health Sciences › Medicine › Surgery › Intraperitoneal and Appendiceal Malignancies
- Keywords
- PEGPH20, metastatic pancreatic cancer, nab-paclitaxel, gemcitabine, combination chemotherapy, overall survival, progression-free survival, objective response rate, hyaluronic acid, tumor microenvironment, drug safety
- MeSH terms
- Progression-Free Survival, Gemcitabine, Aged, Albumins, Antineoplastic Combined Chemotherapy Protocols, Deoxycytidine, Double-Blind Method, Fatigue, Female, Humans, Hyaluronic Acid, Hyaluronoglucosaminidase, Hyponatremia, Male, Middle Aged, Pancreatic Neoplasms, Spasm, Survival Rate, Paclitaxel, Disease Progression, Carcinoma, Pancreatic Ductal, Response Evaluation Criteria in Solid Tumors
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