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01-01-2013 | 2012 SSAT Plenary Presentation

Addition of Algenpantucel-L Immunotherapy to Standard Adjuvant Therapy for Pancreatic Cancer: a Phase 2 Study

Authors: Jeffrey M. Hardacre, Mary Mulcahy, William Small, Mark Talamonti, Jennifer Obel, Smitha Krishnamurthi, Caio S. Rocha-Lima, Howard Safran, Heinz-Joseph Lenz, E. Gabriela Chiorean

Published in: Journal of Gastrointestinal Surgery | Issue 1/2013

Abstract

Background

Despite continued investigation, limited progress has been made in the adjuvant treatment of resected pancreatic cancer. Novel or targeted therapies are needed.

Methods

Multi-institutional, open-label, dose-finding, phase 2 trial evaluating the use of algenpantucel-L (NewLink Genetics Corporation, Ames, IA) immunotherapy in addition to chemotherapy and chemoradiotherapy in the adjuvant setting for resected pancreatic cancer (ClinicalTrials.gov identifier, NCT00569387). The primary outcome was 12-month disease-free survival. Secondary outcomes included overall survival and toxicity.

Results

Seventy patients were treated with gemcitabine and 5-fluorouracil-based chemoradiotherapy as well as algenpantucel-L (mean 12 doses, range 1–14). After a median follow-up of 21 months, the 12-month disease-free survival was 62 %, and the 12-month overall survival was 86 %. The most common adverse events were injection site pain and induration.

Conclusions

The addition of algenpantucel-L to standard adjuvant therapy for resected pancreatic cancer may improve survival. A multi-institutional, phase 3 study is ongoing (ClinicalTrials.gov identifier, NCT01072981).

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Kalser MH, Ellenber SS. Pancreatic Cancer: Adjuvant Combined Radiation and Chemotherapy Following Curative Resection. Arch Surg 1985;120:899–903.PubMedCrossRef

Klinkenbijl JH, Jeekel J, Sahmoud T, et al. Adjuvant Radiotherapy and 5-fluorouracil after Curative Resection of Cancer of the Pancreas and Periampullary Region: Phase III Trial of the EORTC Gastrointestinal Tract Cancer Cooperative Group. Ann Surg 1999;230:776–82.PubMedCrossRef

Neoptolemos JP, Dunn JA, Stocken DD, et al. Adjuvant Chemoradiotherapy and Chemotherapy in Resectable Pancreas Cancer: A Randomised Controlled Trial. Lancet 2001;358:1576–1585.PubMedCrossRef

Oettle H, Post S, Neuhaus P, et al. Adjuvant Chemotherapy with Gemcitabine vs. Observation in Patients Undergoing Curative-intent Resection of Pancreatic Cancer: A Randomized Controlled Trial. JAMA 2007;297:267–77.PubMedCrossRef

Regine WF, Winter KA, Abrams RA, et al. Fluorouracil vs. Gemcitabine Chemotherapy Before and After Fluorouracil-Based Chemoradiation Following Resection of Pancreatic Adenocarcinoma: A Randomized Controlled Trial. JAMA 2008;299:1019–26.PubMedCrossRef

Neoptolemos JP, Stocken DD, Bassi C, et al. Adjuvant Chemotherapy with Fluorouracil plus Folinic Acid vs. Gemcitabine Following Pancreatic Cancer Resection: A Randomized Controlled Trial. JAMA 2010;304:1073–81.PubMedCrossRef

National Comprehensive Cancer Network Guidelines Version 2.2012—Pancreatic Adenocarcinoma. Available at: www.nccn.org. Accessed 15 March 2012

Joziasse DH, Oriol R. Xenotransplantation: the Importance of the Galα1,3Gal Epitope in Hyperacute Vascular Rejection. Biochim Biophy Acta 1999;1455:403–18.CrossRef

Galili U, Mandrell RE, Hamadeh RM, et al. Interaction between Human Natural Anti-alpha-galactosyl Immunoglobulin G and Bacteria of the Human Flora. Infect Immun 1988;56:1730–37.PubMed

10.

Baumann BC, Forte P, Hawley RJ, et al. Lack of Galactose-α-1,3-galactose Expression on Porcine Endothelial Cells Prevents Complement-induced Lysis but not Direct Xenogenic NK Cytotoxicity. J Immunol 2004;172:6460–7.PubMed

11.

Schaapherder AF, Daha MR, te Bulte MT, et al. Antibody-dependent cell-mediated cytotoxicity against porcine endothelium induced by a majority of human sera. Transplantation 1994;57:1376–82.PubMedCrossRef

12.

Watier H, Guillaumin JM, Vallee I, et al. Human NK cell-mediated direct and IG-dependent Cytotoxicity against Xenogeneic Porcine Epithelial Cells. Transpl Immunol 1996;4:293–9.PubMedCrossRef

13.

Watier H, Giollaumin JM, Piller F, et al. Removal of Terminal α-galactosyl Residues from Xenogeneic Porcine Endothelial Cells. Decrease in Complement-mediated cytotoxicity but Persistence of IgG1-mediated Antibody-dependent Cell-mediated Cytotoxicity. Transplantation 1996;62:105–13.PubMedCrossRef

14.

Bilimoria KY, Bentrem DJ, Ko CY, et al. Validation of the 6th Edition AJCC Pancreatic Cancer Staging System: Report from the National Cancer Database. Cancer 2007;110:738–44.PubMedCrossRef

15.

Brennan MF, Kattan MW, Klimstra D, Conlon K. Prognostic Nomogram for Patients Undergoing Resection for Adenocarcinoma of the Pancreas. Ann Surg 2004;240:293–8.PubMedCrossRef

16.

Zitvogel L, Apetoh L, Ghiringhelli F, et al. The Anticancer Immune Response: Indispensable for Therapeutic Success? J Clin Invest 2008;118:1991–2001.PubMedCrossRef

17.

Lutz E, Yeo CJ, Lillemoe KD, et al. A Lethally Irradiated Allogeneic Granulocyte-Macrophage Colony Stimulating Factor-Secreting Tumor Vaccine for Pancreatic Adenocarcinoma: A Phase II Trial of Safety, Efficacy, and Immune Activation. Ann Surg 2011;253:328–35.PubMedCrossRef

18.

Abou-Alfa GK, Chapman PB, Feilchenfeldt J, et al. Targeting Mutated K-ras in Pancreatic Adenocarcinoma Using an Adjuvant Vaccine. Am J Clin Oncol 2011;34:321–5.PubMedCrossRef

19.

Morse MA, Nair SK, Boczkowski D, et al. The Feasibility and Safety of Immunotherapy with Dendritic Cells Loaded with CEA mRNA Following Neoadjuvant Chemoradiotherapy and Resection of Pancreatic Cancer. Int J Gastrointest Cancer 2002;32:1–6.PubMedCrossRef

20.

Ramanathan RK, Lee KM, McKolanis J, et al. Phase I Study of a MUC1 Vaccine Composed of Different Doses of MUC1 Peptide with SB-A2 Adjuvant in Resected and Locally Advanced Pancreatic Cancer. Cancer Immunol Immunother 2005;54:254–64.PubMedCrossRef

21.

Maki RG, Livingston PO, Lewis JJ, et al. A Phase I Pilot Study of Autologous Heat Shock Protein Vaccine HXPPC-96 in Patients with Resected Pancreatic Adenocarcinoma. Dig Dis Sci 2007;52:1964–72.PubMedCrossRef

Title: Addition of Algenpantucel-L Immunotherapy to Standard Adjuvant Therapy for Pancreatic Cancer: a Phase 2 Study
Authors: Jeffrey M. Hardacre
Mary Mulcahy
William Small
Mark Talamonti
Jennifer Obel
Smitha Krishnamurthi
Caio S. Rocha-Lima
Howard Safran
Heinz-Joseph Lenz
E. Gabriela Chiorean
Publication date: 01-01-2013
Publisher: Springer-Verlag
Published in: Journal of Gastrointestinal Surgery / Issue 1/2013
Print ISSN: 1091-255X
Electronic ISSN: 1873-4626
DOI: https://doi.org/10.1007/s11605-012-2064-6

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Addition of Algenpantucel-L Immunotherapy to Standard Adjuvant Therapy for Pancreatic Cancer: a Phase 2 Study

Abstract

Background

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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