ArticleOA
作者: Fink, Karen L ; Goldlust, Samuel A ; Salacz, Michael ; Lindhorst, Scott ; Prins, Robert M ; New, Pamela Z ; Heth, Jason A ; Cobbs, Charles S ; Wu, Julian ; May, Sven-Axel ; Maida, Anthony E ; Kim, Lyndon J ; Sloan, Andrew E ; Thompson, Reid C ; Pillainayagam, Clement P ; Moshel, Yaron A ; Abram, Steven R ; Khagi, Simon ; Walter, Kevin A ; Krex, Dietmar ; Dropcho, Edward J ; Piccioni, David ; Trusheim, John E ; Brem, Steven ; Duma, Christopher ; Pearlman, Michael ; Ashkan, Keyoumars ; Pluard, Timothy J ; Lillehei, Kevin O ; Iwamoto, Fabio M ; Bota, Daniela A ; Cloughesy, Timothy F ; Loudon, William G ; Mulholland, Paul ; Etame, Arnold B ; Bosch, Marnix L ; Mathieu, David ; Taylor, Sarah ; Portnow, Jana ; Taylor, Lynne P ; Villano, John L ; Westphal, Manfred ; Baskin, David S ; Elinzano, Heinrich ; Aiken, Robert ; Liau, Linda M ; Mikkelsen, Tom ; Geoffroy, Francois J ; Tse, Victor ; Lutzky, Jose ; Schackert, Gabriele ; Kesari, Santosh ; Avigan, David E ; Petrecca, Kevin ; Toms, Steven A ; Green, Richard M ; Grewal, Jai ; Meisel, Hans-Jorg ; Ewend, Matthew G ; Schulder, Michael ; Tran, David D ; Duic, Paul ; Chaudhary, Rekha ; Brenner, Andrew J ; Lacroix, Michel ; Walbert, Tobias ; Davis, Raphael P ; Campian, Jian L ; D'Andre, Stacy D
AbstractBackgroundStandard 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