Combining an autologous dendritic cell-based immunotherapy (DCVAC/PCa) with chemotherapy did not improve overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC), when compared with placebo plus chemotherapy, according to results of the phase 3 VIABLE study published in JAMA Oncology.
The median OS was 23.9 months in patients who received DCVAC/PCa plus chemotherapy (docetaxel-prednisone), and 24.3 months in those who received placebo plus chemotherapy (hazard ratio [HR], 1.04; 95% CI, 0.90-1.21; P =.60).
VIABLE was a double-blind, multicenter phase 3 trial (ClinicalTrials.gov Identifier: NCT02111577) designed to test the hypothesis that combining docetaxel with DCVAC/PCa followed by maintenance therapy with DCVAC/PCa would improve OS in patients with mCRPC.
The study enrolled 1182 patients with mCRPC who had a median age of 68 years (range, 46 to 89). The participants were randomly assigned 2:1 to receive DCVAC/PCa as add-on and maintenance (n=787) or placebo (n=395), both in combination with chemotherapy. Approximately 82% of patients started DCVAC/PCa, and approximately 98% started placebo.
In abiraterone- and enzalutamide-naive patients (n=817), there was no difference in the median OS between the DCVAC/PCa and placebo arms — 26.7 months and 25.7 months, respectively (HR, 0.94; 95% CI, 0.78-1.13; P =.50).
Among patients who previously received abiraterone and/or enzalutamide (n=365), the median OS was 16 months in the DCVAC/PCa arm and 21.0 months in the placebo arm (HR, 1.28; 95% CI, 0.98-1.67; P =.07).
There were no significant differences in any secondary efficacy endpoints, including radiological progression-free survival, time to prostate-specific antigen progression, or skeletal-related events between the 2 arms.
Post hoc analyses in subgroups of patients receiving different doses of DVAC/PCa or placebo showed a trend in median OS suggestive of a treatment effect with increasing drug exposure. With 10 or more doses, the median OS was 31.5 months with DVAC/PCa and 27.0 months with placebo (HR, 0.92; 95% CI, 0.74-1.15; P =.48).
With 12 or more doses, the median OS was 35.9 months for DVAC/PCa and 29.8 months for placebo (HR, 0.77; 95% CI, 0.60-1.00; P =.05). With 15 doses, the median OS was 41.2 months for DVAC/PCa and 38.7 months for placebo (HR, 0.72; 95% CI, 0.49-1.06; P =.09).
Treatment-emergent adverse events (TEAEs) were observed in 9.2% of patients in the DCVAC/PCa arm and 12.7% of patients in the placebo arm. The most common TEAEs (with DCVAC/PCa and placebo, respectively) were fatigue (36.2% vs 40.1%), alopecia (29.6% vs 34.3%), and diarrhea (27.5% vs 30.9%).
“DCVAC/PCa combined with docetaxel plus prednisone and continued as maintenance treatment did not extend OS,” but was well tolerated in patients with mCRPC, the researchers concluded. “Factors associated with the efficacy of immunotherapy should be identified to better select patients and thus prolong OS.”
Disclosures: This research was supported by Sotio. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Vogelzang NJ, Beer TM, Gerritsen W, et al. Efficacy and safety of autologous dendritic cell-based immunotherapy, docetaxel, and prednisone vs placebo in patients with metastatic castration-resistant prostate cancer: The VIABLE phase 3 randomized clinical trial. JAMA Oncol. Published online February 10, 2022. doi:10.1001/jamaoncol.2021.7298