No overall survival (OS) benefit was seen for patients with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (CRPC) treated with the prostate-specific antigen (PSA)-targeted, poxvirus-based cancer vaccine PROSTVAC-V/F (PRO) compared with placebo, according to results of the PROSPECT trial (abstract 5006).
PROSPECT was designed to be a confirmatory trial conducted following a phase II trial that showed an 8.5-month improvement in overall survival (OS) with PRO compared with placebo. However, after a third interim analysis, the data monitoring committee recommended closure of PROSPECT on the grounds of futility.
The results were presented by James L. Gulley, MD, of the National Cancer Institute, at the 2018 Annual Society of Clinical Oncology (ASCO) Annual Meeting, held June 1–5 in Chicago.
PROSPECT randomly assigned 1,297 patients with asymptomatic or minimally symptomatic metastatic CRPC to one of three arms: PRO plus placebo, PRO plus granulocyte-macrophage colony-stimulating factor (GM-CSF), or double placebo. The vaccine was given in week 1, and patients received six subsequent boost vaccinations over a period of 5 months. OS was the primary endpoint.
Patients received most treatments though week 13, with a slight decrease thereafter. At the time of the third interim analysis, the OS curves for the intent-to-treat population overlapped. The hazard ratio (HR) for PROSTVAC compared with placebo was 1.0058; for PROSTVAC plus GM-CSF compared with placebo, HR was 1.0202. Median OS was between 33.2 months and 34.4 months.
“The overall survival observed in all arms was approximately 1 year longer than anticipated based on historical controls and the prior randomized phase II trial,” Gulley said. “This was likely due to improved standard of care as study enrollment began in 2011.”
In a subgroup analysis, the researchers found no difference between the treatment arms for any of the groups analyzed. In addition, there was no difference between study arms for event-free survival, a secondary endpoint.
Toxicity was also similar between the groups of patients. Common adverse events included injection site reactions, fatigue, chills, influenza-like illness, and pyrexia. Pyrexia and injection site reaction were slightly more common among patients who received GM-CSF. Serious treatment-emergent adverse events were seen in less than 1% of patients.
Discussing the results of the trial, Douglas G. McNeel, MD, PhD, of the University of Wisconsin School of Medicine and Public Health, asked, “What happened here?”
“There was a lot of excitement about this trial based on the phase II trial from 2010 which showed a very significant difference in overall survival between these groups,” McNeel said. “If you look at that trial compared with what you currently see, the control population was markedly different and had almost a doubling of overall survival. The fact is that things have changed since 2010.”
Daniel G. Chong, MD, of Virginia Cancer Specialists, Fairfax, Va., commented, "This is yet another promising study demonstrating that using the immune system to treat advanced prostate cancer does not produce the same effectiveness as is seen in other cancer types, and we may need to use other techniques to make prostate cancer more immunogenic to checkpoint inhibitors and vaccines."