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.”
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.
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.
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.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.