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.
Recommended CitationLiau, 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; Walpert, 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., "First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma." (2018). Department of Medical Oncology Faculty Papers. Paper 82.
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