Title |
First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma
|
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Published in |
Journal of Translational Medicine, May 2018
|
DOI | 10.1186/s12967-018-1507-6 |
Pubmed ID | |
Authors |
Linda M. Liau, Keyoumars Ashkan, David D. Tran, Jian L. Campian, John E. Trusheim, Charles S. Cobbs, Jason A. Heth, Michael Salacz, Sarah Taylor, Stacy D. D’Andre, Fabio M. Iwamoto, Edward J. Dropcho, Yaron A. Moshel, Kevin A. Walter, Clement P. Pillainayagam, Robert Aiken, Rekha Chaudhary, Samuel A. Goldlust, Daniela A. Bota, Paul Duic, Jai Grewal, Heinrich Elinzano, Steven A. Toms, Kevin O. Lillehei, Tom Mikkelsen, Tobias Walbert, Steven R. Abram, Andrew J. Brenner, Steven Brem, Matthew G. Ewend, Simon Khagi, Jana Portnow, Lyndon J. Kim, William G. Loudon, Reid C. Thompson, David E. Avigan, Karen L. Fink, Francois J. Geoffroy, Scott Lindhorst, Jose Lutzky, Andrew E. Sloan, Gabriele Schackert, Dietmar Krex, Hans-Jorg Meisel, Julian Wu, Raphael P. Davis, Christopher Duma, Arnold B. Etame, David Mathieu, Santosh Kesari, David Piccioni, Manfred Westphal, David S. Baskin, Pamela Z. New, Michel Lacroix, Sven-Axel May, Timothy J. Pluard, Victor Tse, Richard M. Green, John L. Villano, Michael Pearlman, Kevin Petrecca, Michael Schulder, Lynne P. Taylor, Anthony E. Maida, Robert M. Prins, Timothy F. Cloughesy, Paul Mulholland, Marnix L. Bosch |
Abstract |
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®-L) to standard therapy for newly diagnosed glioblastoma. 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). 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. 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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 52 | 29% |
United Kingdom | 14 | 8% |
Canada | 6 | 3% |
Hong Kong | 4 | 2% |
Australia | 3 | 2% |
South Africa | 1 | <1% |
Hungary | 1 | <1% |
Spain | 1 | <1% |
Trinidad and Tobago | 1 | <1% |
Other | 9 | 5% |
Unknown | 90 | 49% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 150 | 82% |
Scientists | 17 | 9% |
Practitioners (doctors, other healthcare professionals) | 9 | 5% |
Science communicators (journalists, bloggers, editors) | 3 | 2% |
Unknown | 3 | 2% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 463 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 59 | 13% |
Student > Ph. D. Student | 53 | 11% |
Student > Bachelor | 53 | 11% |
Student > Master | 45 | 10% |
Student > Doctoral Student | 30 | 6% |
Other | 81 | 17% |
Unknown | 142 | 31% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 88 | 19% |
Biochemistry, Genetics and Molecular Biology | 55 | 12% |
Neuroscience | 43 | 9% |
Immunology and Microbiology | 33 | 7% |
Agricultural and Biological Sciences | 26 | 6% |
Other | 61 | 13% |
Unknown | 157 | 34% |