KEY TAKEAWAYS
- The phase 3 trial investigating the efficacy of adding autologous tumor lysate-loaded DCVax-L to SOC for nGBM and rGBM patients.
- The trial was conducted at 94 sites in 4 countries and enrolled 331 patients. Of these, 232 were randomized to the DCVax-L group and 99 to the placebo group.
- Results showed that mOS for patients with nGBM receiving DCVax-L was 19.3 months compared to 16.5 months in control patients. For patients with rGBM receiving DCVax-L, mOS was 13.2 months compared to 7.8 months in control patients.
- The survival benefit was even greater in patients with nGBM with methylated MGMT receiving DCVax-L compared with external control patients.
- Adding DCVax-L to SOC resulted in a clinically meaningful and statistically significant extension of survival for patients with both nGBM and rGBM compared with contemporaneous, matched external controls who received SOC alone.
The most deadly kind of primary brain cancer is glioblastoma. The clinical outcomes for glioblastoma remain dismal, highlighting the need for novel treatments. This study aims to determine whether combining standard of care (SOC) with a dendritic cell vaccine (DCVax-L) loaded with autologous tumor lysate improves survival in patients with glioblastoma.
Overall survival (OS) was compared between patients with newly diagnosed glioblastoma (nGBM) and recurrent glioblastoma (rGBM) treated with DCVax-L plus SOC and contemporaneous matched external control patients treated with SOC in this phase 3, prospective, externally controlled nonrandomized trial. From August 2007 through November 2015, 94 locations across 4 nations participated in this international, multicenter experiment.
The time of analysis was from October 2020 through September 2021. This study combined DCVax-L with SOC temozolomide as the active therapy. Those with nGBM were given SOC temozolomide and a placebo, whereas those with rGBM were given standard rGBM treatments. Overall survival (OS) in nGBM and rGBM were compared to contemporary matched external control populations from the control groups of other formal randomized clinical trials as the primary and secondary end goals, respectively.
In all, 331 participants were included in the study, with 232 assigned to receive DCVax-L and 99 assigned to receive a placebo. For the 232 patients with nGBM who received DCVax-L, the median overall survival (mOS) was 19.3 (95% CI, 17.5-21.3) months after randomization (22.4 months from surgery), compared to 16.5 (95% CI, 16.0-17.5) months in the control group (HR = 0.80; 98% CI, 0.00-0.94; P =.002). When comparing survival rates at 48 months and 60 months after randomization, the former was 15.7%, and the latter was 9.9%. The median overall survival (mOS) for the 64 patients with rGBM who received DCVax-L was 13.2 (95% CI, 9.7-16.8) months, compared to 7.8 (95% CI, 7.2-8.2) months for the control patients (HR, 0.58; 98% CI, 0.00-0.76; P< .001).
About 27 percent versus 9.6 percent and eleven point one percent versus five point one percent survival was seen at 24 and 30 months after recurrence, respectively. Patients with nGBM and methylated MGMT who received DCVax-L had a longer overall survival time compared to patients in the control group (HR, 0.74; 98% CI, 0.55-1.00; P =.03). In this study, patients with nGBM and rGBM who got DCVax-L in addition to SOC had a statistically and clinically significant longer survival time compared to contemporary, matched controls who received SOC alone.
Source: https://pubmed.ncbi.nlm.nih.gov/36394838/
Clinical trial: https://clinicaltrials.gov/ct2/show/NCT00045968
Liau, L.M., Ashkan, K., Brem, S., Campian, J.L., Trusheim, J.E., Iwamoto, F.M., Tran, D.D., Ansstas, G., Cobbs, C.S., Heth, J.A., Salacz, M.E., D’Andre, S., Aiken, R.D., Moshel, Y.A., Nam, J.Y., Pillainayagam, C.P., Wagner, S.A., Walter, K.A., Chaudary, R. and Goldlust, Lee I, Bota S, Elinzano H, Grewal J, Lillehei K, Mikkelsen T, Walbert T, Abram S, Brenner A, Ewend M, Khagi S, Locick D, Portnow J, Lim L, Loudon W, Martinez N, Thompson R, Avigan D, Fink K, Geoffroy F, Giglio P, Gligich O, Krex D, Lindhorst S, Lutzky J, Meisel HJ, Nadji-Ohl M, Sanchin L, Sloan A, Taylor L, Wu J, Dunbar E, Etame A, Kesari S, Mathieu D, Piccioni D, Baskin D, Lacroix M, May SA, New P, Pluard T, Toms S, Tse V, Peak S, Villano J, Battiste J, Mulholland P, Pearlman M, Petrecca K, Schulder M, Prins R, Boynton A, Bosch M (2022). Association of Autologous Tumor Lysate-Loaded Dendritic Cell Vaccination With Extension of Survival Among Patients With Newly Diagnosed and Recurrent Glioblastoma. JAMA Oncology. doi:https://doi.org/10.1001/jamaoncol.2022.5370.
