1. First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma
- Author
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Liau, Linda M, Ashkan, Keyoumars, Tran, David D, Campian, Jian L, Trusheim, John E, Cobbs, Charles S, Heth, Jason A, Salacz, Michael, Taylor, Sarah, D’Andre, Stacy D, Iwamoto, Fabio M, Dropcho, Edward J, Moshel, Yaron A, Walter, Kevin A, Pillainayagam, Clement P, Aiken, Robert, Chaudhary, Rekha, Goldlust, Samuel A, Bota, Daniela A, Duic, Paul, Grewal, Jai, Elinzano, Heinrich, Toms, Steven A, Lillehei, Kevin O, Mikkelsen, Tom, Walbert, Tobias, Abram, Steven R, Brenner, Andrew J, Brem, Steven, Ewend, Matthew G, Khagi, Simon, Portnow, Jana, Kim, Lyndon J, Loudon, William G, Thompson, Reid C, Avigan, David E, Fink, Karen L, Geoffroy, Francois J, Lindhorst, Scott, Lutzky, Jose, Sloan, Andrew E, Schackert, Gabriele, Krex, Dietmar, Meisel, Hans-Jorg, Wu, Julian, Davis, Raphael P, Duma, Christopher, Etame, Arnold B, Mathieu, David, Kesari, Santosh, Piccioni, David, Westphal, Manfred, Baskin, David S, New, Pamela Z, Lacroix, Michel, May, Sven-Axel, Pluard, Timothy J, Tse, Victor, Green, Richard M, Villano, John L, Pearlman, Michael, Petrecca, Kevin, Schulder, Michael, Taylor, Lynne P, Maida, Anthony E, Prins, Robert M, Cloughesy, Timothy F, Mulholland, Paul, and Bosch, Marnix L
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Immunology ,Prevention ,Orphan Drug ,Clinical Research ,Vaccine Related ,Rare Diseases ,Immunization ,Neurosciences ,Brain Disorders ,Cancer ,Clinical Trials and Supportive Activities ,Brain Cancer ,Patient Safety ,6.1 Pharmaceuticals ,Adult ,Aged ,Brain Neoplasms ,Cancer Vaccines ,Dendritic Cells ,Endpoint Determination ,Female ,Glioblastoma ,Humans ,Male ,Middle Aged ,Prognosis ,Survival Analysis ,Treatment Outcome ,Young Adult ,Immunotherapy ,Dendritic cell ,Vaccine ,Medical and Health Sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
BackgroundStandard 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.MethodsAfter 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).ResultsFor 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.ConclusionsAddition 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.
- Published
- 2018