Nicholas J. Vogelzang, MD
In a phase III trial (VIABLE) reported in JAMA Oncology, Nicholas J. Vogelzang, MD, and colleagues found that the addition of an autologous dendritic cell–based immunotherapy directed against prostate cancer (DCVAC/PCa) to chemotherapy did not improve overall survival in metastatic castration-resistant prostate cancer.
As stated by the investigators: “DCVAC/PCa is an active cellular immunotherapy designed to initiate an immune response against prostate cancer…. Dendritic cells prepared from a patient’s monocytes are collected by leukapheresis and subsequently exposed to a human prostate adenocarcinoma cell line killed by immunogenic modality.”
Study Details
KEY POINTS
- The addition of DCVAC/PCa to chemotherapy with DCVAC/PCa maintenance did not improve overall survival.
- A potential treatment effect was observed with increasing number of DCVAC/PCa doses received.
In the double-blind trial, 1,182 patients from sites in the United States and Europe were randomly assigned 2:1 between June 2014 and November 2017 to receive DCVAC/PCa plus chemotherapy followed by DCVAC/PCa maintenance (n = 787) or placebo plus chemotherapy followed by placebo maintenance (n = 395). DCVAC/PCa or placebo was administered subcutaneously every 3 to 4 weeks for up to 15 doses. Chemotherapy was started 3 days after leukapheresis and consisted of docetaxel at 75 mg/m2 at 3-week intervals and prednisone at 5 mg orally twice daily for up to 10 cycles. DCVAC/PCa or placebo treatment started approximately 5 weeks after leukapheresis and more than 7 days after the second dose of docetaxel. The primary endpoint was overall survival in all randomized patients.
Overall Survival
Among the total of 1,182 randomized patients, 610 (81.8%) started DCVAC/PCa and 376 (98.4%) started placebo. A total of 136 patients did not start DCVAC/PCa, 119 due to production failures and 19 for other reasons.
Among all randomized patients, median overall survival was 23.9 months (95% confidence interval [CI] = 21.6–25.3 months) in the DCVAC/PCa group vs 24.3 months (95% CI = 22.6–26.0 months) in the control group (hazard ratio [HR] = 1.04, 95% CI = 0.90–1.21, P = .60).
Post hoc analyses suggested a treatment effect with increasing number of DCVAC/PCa and placebo doses received: median overall survival was 31.5 vs 27.0 months (HR = 0.92, P = .48) with at least 10 doses, 35.9 vs 29.8 months (HR = 0.77, P = .05) with at least 12 doses, and 41.2 vs 38.7 months (HR = 0.72, P = .09) with 15 doses received.
Approximately 70% of patients had not previously received abiraterone or enzalutamide. Among 817 abiraterone- and enzalutamide-naive patients, median overall survival was 26.7 vs 25.7 months (HR = 0.94, P = .50); among 365 patients pretreated with abiraterone or enzalutamide, median overall survival was 16 vs 21.0 months (HR = 1.28, P = .07).
No differences between groups were observed in radiologic progression-free survival, time to prostate-specific antigen progression, or skeletal-related events.
Adverse Events
The most common adverse events of any grade in the DCVAC/PCa vs placebo groups were fatigue (36.2% vs 40.1%), alopecia (29.6% vs 34.3%), and diarrhea (27.5% vs 30.9%). Grade ≥ 3 adverse events occurred in 50.1% vs 57.0%. Adverse events of any grade considered related to DCVAC/PCa vs placebo occurred in 9.2% vs 12.7%. Adverse events of any grade considered related to chemotherapy occurred in 80.0% vs 87.7%. Skeletal-related events occurred in 5.5% vs 6.6%. Serious adverse events occurred in 31.6% vs 39.6%. Adverse events led to discontinuation of DCVAC/PCa in 4.1% and chemotherapy in 13.5% of the DCVAC/PCa group and to discontinuation of placebo in 3.4% and chemotherapy in 14.5% of the control group. Adverse events led to death in 5.2% vs 7.9% of patients.
The investigators concluded: “In this phase 3 randomized clinical trial, DCVAC/PCa combined with docetaxel plus prednisone and continued as maintenance treatment did not extend [overall survival] in patients with [metastatic castration-resistant prostate cancer] and was well tolerated.”
Dr. Vogelzang, of Comprehensive Cancer Centers of Nevada, Las Vegas, is the corresponding author of the JAMA Oncology article.
Disclosure: The study was funded by Sotio a.s. For full disclosures of the study authors, visit jamanetwork.com.
