Authors

Linda M. Liau, University of California Los Angeles
Keyoumars Ashkan, King's College London
David D. Tran, University of Florida
Jian L. Campian, Washington University, St. Louis
John E. Trusheim, Abbott Northwestern Hospital
Charles S. Cobbs, Swedish Neuroscience Institute
Jason A. Heth, The University Of Michigan
Michael Salacz, University of Kansas Cancer Center
Sarah Taylor, University of Kansas Cancer Center
Stacy D. D'Andre, Sutter Institute for Medical Research
Fabio M. Iwamoto, Columbia University Medical Center
Edward J. Dropcho, Indiana University Simon Cancer Center
Yaron A. Moshel, Overlook Medical Center
Kevin A. Walter, University of Rochester Medical Center
Clement P. Pillainayagam, Rush University Medical Center
Robert Aiken, Rutgers Cancer Institute
Rekha Chaudhary, University of Cincinnati Medical Center
Samuel A. Goldlust, Hackensack University Medical Center
Daniela A. Bota, UC Irvine Medical Center
Paul Duic, Winthrop-University Hospital
Jai Grewal, NYU Winthrop Hospital
Heinrich Elinzano, Rhode Island Hospital
Steven A. Toms, Rhode Island Hospital
Kevin O. Lillehei, University of Colorado Hospital
Tom Mikkelsen, Henry Ford Health System
Tobias Walpert, Henry Ford Health System
Steven R. Abram, St. Thomas Research Institute
Andrew J. Brenner, University of Texas Health Science Center, San Antonio
Steven Brem, University of Pennsylvania
Matthew G. Ewend, University of North Carolina, Chapel Hill
Simon Khagi, University of North Carolina, Chapel Hill
Jana Portnow, City of Hope National Medical Center
Lyndon J. Kim, Thomas Jefferson UniversityFollow
William G. Loudon, St. Joseph Hospital, Newport Beach
Reid C. Thompson, Vanderbilt University
David E Avigan, Beth Israel Deaconess Medical Center
Karen L. Fink, Baylor University Medical Center
Francois J. Geoffroy, Illinois CancerCare
Scott Lindhorst, Medical University of South Carolina
Jose Lutzky, Mount Sinai Comprehensive Cancer Center
Andrew E. Sloan, University Hospitals Case Medical Center
Gabriele Schackert, University Hospital Carl-Gustav-Carus of Technical University
Dietmar Krex, University Hospital Carl-Gustav-Carus of Technical University
Hans-Jorg Meisel, BG-Klinikum Bergmannstrost
Julian Wu, Tufts University School of Medicine
Raphael P Davis, Stony Brook University
Christopher Duma, Hoag Cancer Center
Arnold B. Etame, H. Lee Moffit Cancer Center and Research Institute
David Mathieu, CHUS-Hopital Fleurimont, Sherbrooke University
Santosh Kesari, UCSD Health System, UC San Diego
David Piccioni, UCSD Health System, UC San Diego
Manfred Westphal, Neurochirurgische Klinik University Clinic Hamburg-Eppendorf
David S. Baskin, Houston Methodist
Pamela Z. New, Houston Methodist
Michel Lacroix, Geisinger Health System
Sven-Axel May, Klinikum Chemnitz GGMBH
Timothy J. Pluard, Saint Luke's Cancer Institute
Victor Tse, Kaiser Permanente Northern California
Richard M. Green, Kaiser Permanente Southern California
John L. Villano, University of Kentucky College of Medicine
Michael Pearlman, Colorado Neurological Institute
Kevin Petrecca, McGill University
Michael Schulder, Northwell Hofstra School of Medicine
Lynne P Taylor, University of Washington
Anthony E. Maida, Northwest Biotherapeutics Inc.
Robert M. Prins, University of California Los Angeles
Timothy F. Cloughesy, University of California Los Angeles
Paul Mulholland, University College Hospitals, London
Marnix L. Bosch, Northwest Biotherapeutics Inc.

Document Type

Article

Publication Date

5-29-2018

Comments

This article has been peer reviewed. It is the author’s final published version in Journal of Translational Medicine, Volume 16, Issue 1, May 2018, Article number 142.

The published version is available at https://doi.org/10.1186/s12967-018-1507-6. Copyright © Liau et al.

Abstract

BACKGROUND: Standard therapy for glioblastoma includes surgery, radiotherapy, and temozolomide. This Phase 3 trial evaluates the addition of an autologous tumor lysate-pulsed dendritic cell vaccine (DCVax

METHODS: After surgery and chemoradiotherapy, patients were randomized (2:1) to receive temozolomide plus DCVax-L (n = 232) or temozolomide and placebo (n = 99). Following recurrence, all patients were allowed to receive DCVax-L, without unblinding. The primary endpoint was progression free survival (PFS); the secondary endpoint was overall survival (OS).

RESULTS: For the intent-to-treat (ITT) population (n = 331), median OS (mOS) was 23.1 months from surgery. Because of the cross-over trial design, nearly 90% of the ITT population received DCVax-L. For patients with methylated MGMT (n = 131), mOS was 34.7 months from surgery, with a 3-year survival of 46.4%. As of this analysis, 223 patients are ≥ 30 months past their surgery date; 67 of these (30.0%) have lived ≥ 30 months and have a Kaplan-Meier (KM)-derived mOS of 46.5 months. 182 patients are ≥ 36 months past surgery; 44 of these (24.2%) have lived ≥ 36 months and have a KM-derived mOS of 88.2 months. A population of extended survivors (n = 100) with mOS of 40.5 months, not explained by known prognostic factors, will be analyzed further. Only 2.1% of ITT patients (n = 7) had a grade 3 or 4 adverse event that was deemed at least possibly related to the vaccine. Overall adverse events with DCVax were comparable to standard therapy alone.

CONCLUSIONS: Addition of DCVax-L to standard therapy is feasible and safe in glioblastoma patients, and may extend survival. Trial registration Funded by Northwest Biotherapeutics; Clinicaltrials.gov number: NCT00045968; https://clinicaltrials.gov/ct2/show/NCT00045968?term=NCT00045968&rank=1 ; initially registered 19 September 2002.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

Language

English

Share

COinS