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®-L) to standard therapy for newly diagnosed glioblastoma.
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.
Digital Object Identifier (DOI)
Funded by Northwest Biotherapeutics; Clinicaltrials.gov number: NCT00045968; https://clinicaltrials.gov/ct2/show/NCT00045968?term=NCT00045968&rank=1; initially registered 19 September 2002.
Supported by Northwest Biotherapeutics, Inc. and the UCLA SPORE in Brain Cancer (P50-CA211015). Northwest Biotherapeutics, Inc. was the trial sponsor and had a role in the design and conduct of the study, along with academic advisers; collection, management, analysis, and interpretation of the data; preparation, review, and approval of the manuscript; and decision to submit the manuscript for publication.
The datasets generated and/or analyzed during the current study are not publicly available to protect future regulatory filings but access to the data can be available through an independent statistician on a case by case basis, as necessary and under confidentiality.
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.; and Villano, John L., "First Results on Survival from a Large Phase 3 Clinical Trial of an Autologous Dendritic Cell Vaccine in Newly Diagnosed Glioblastoma" (2018). Internal Medicine Faculty Publications. 145.