medwireNews: The active autologous dendritic cell-based immunotherapy DCVAC/PCa is well tolerated when combined with docetaxel plus prednisone but does not improve survival in men with metastatic castration-resistant prostate cancer (mCRPC), phase 3 study data show.
Nicholas Vogelzang (Comprehensive Cancer Centers of Nevada, Las Vegas, USA) and co-investigators from the VIABLE trial say that “factors associated with the efficacy of immunotherapy should be identified to better select patients and thus prolong OS [overall survival].”
The researchers explain that DCVAC/PCa (also known as stapuldencel) is prepared using leukapheresis to collect dendritic cells prepared from the patient’s monocytes, which are then exposed to a human prostate adenocarcinoma cell line killed by immunogenic modality.
They hypothesized that the treatment would “deliver prostate cancer antigens for effective in vivo T-cell activation to mount an immune response against the tumor, resulting in tumor regression and prolonging OS.”
To test this hypothesis, 1182 men (median age, 68 years) with mCRPC from 177 hospitals in the USA and Europe were randomly assigned to receive subcutaneous DCVAC/PCa (n=787) or placebo (n=395) each in combination with docetaxel plus prednisone. DCVAC/PCa or placebo was initiated approximately 5 weeks after leukapheresis and more than 7 days after the second dose of docetaxel.
The first nine doses of DCVAC/PCa or placebo were given in 3–4-week intervals alongside chemotherapy, and the remaining six doses were given as maintenance therapy at 4-week intervals.
At the time of the primary analysis, 64.2% of men in the DCVAC/PCa group and 64.3% of those in placebo group had died. There was no significant difference in median OS between the groups, at a respective 23.9 and 24.3 months.
The researchers note in JAMA Oncology, that DCVAC/PCa could not be produced for 119 patients. Nonetheless, when these participants were excluded from the analysis, along with those who had major protocol violations, and participants who received fewer than eight doses of DCVAC/PCa or placebo, there was still no significant difference in median OS between the two groups, at 29.7 and 26.7 months, respectively.
There was, however, a larger, but still nonsignificant difference in OS with use of DCVAC/PCa or placebo among the 365 patients who had previously received abiraterone and/or enzalutamide, at a median of 16.0 versus 21.0 months.
Vogelzang et al also report that “DCVAC/PCa was well tolerated without any observed systemic adverse effects.”
The rate of treatment-emergent adverse events was lower with DCVAC/PCa plus docetaxel (9.2% of 749) than with docetaxel–placebo (12.7% of 379) and the most common events were fatigue (36.2 vs 40.1%), alopecia (29.6 vs 34.3%), and diarrhea (27.5 vs 30.9%).
In an accompanying editorial, Hiten Patel and Stephanie Berg, both from Loyola University Medical Center in Maywood, Illinois, say: “While the results of VIABLE combining stapuldencel-T and docetaxel for mCRPC are disappointing, other combination options involving active cellular immunotherapy or further improvements in technology may hold promise in the future.”
They add: “As the future of clinical trial design for mCRPC gets more complicated, acknowledging negative trials is important because they can spur thought and guide development that may ultimately lead us down more fruitful pathways to effective therapies.”
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group
JAMA Oncol 2022; doi:10.1001/jamaoncol.2021.7298
JAMA Oncol 2022; doi:10.1001/jamaoncol.2021.7282