Men with asymptomatic or minimally symptomatic metastatic castrate-resistant prostate cancer who had baseline prostate-specific antigen levels ≤5.27 ng/mL demonstrated a median overall survival approaching 4 years with sipuleucel-T treatment, according to findings from the large real-world PROCEED trial.
Celestia S. Higano, MD, FACP
Men with asymptomatic or minimally symptomatic metastatic castrate-resistant prostate cancer (mCRPC) who had baseline prostate-specific antigen (PSA) levels ≤5.27 ng/mL demonstrated a median overall survival (OS) approaching 4 years with sipuleucel-T (Provenge) treatment, according to findings from the large real-world PROCEED trial.1,2
“The median survival of 4 years following treatment with Provenge is meaningful,” said Celestia S. Higano, MD, FACP, lead author of the PROCEED analysis, and professor, Division of Medical Oncology, Department of Medicine, University of Washington School of Medicine and Fred Hutchinson Cancer Research Center, in a statement. “PROCEED provides a real-world portrait of the expected OS after sipuleucel-T in [patients with] mCRPC in the modern era of 5 additional life-prolonging agents.”
The multicenter, open-label, observational registry study aimed to analyze real-world efficacy outcomes of patients with mCRPC treated with sipuleucel-T at a time of rapidly evolving treatment options.
A total of 1976 patients with mCRPC were enrolled across 192 urology and medical oncology clinics at both community and academic centers; 1902 patients treated with ≥1 infusion were included in the safety population. Ninety-five percent of the patients received 3 infusions of sipuleucel-T and 2% received only 1 infusion.
The median age of patients was 72 years (range, 42-97) and the median baseline PSA level was 15.0 ng/mL (range, 5.2-46.1). More than half of patients (50.6%) had a Gleason sum of ≥8 and most patients (88.4%) had a low comorbidity index.
After a median follow-up of 46.6 months, during which time 66.0% of patients died, the overall median OS was 30.7 months (95% CI, 28.6-32.2). The median time to prostate cancerrelated death was 42.7 months (95% CI, 39.4-46.2).
A post-hoc analysis examined the OS according to baseline PSA ranges and determined that the median OS was longer among patients in the lowest baseline PSA quartile of ≤5.27 ng/mL. Among patients with a PSA between 5.27 and ≤15.08 ng/mL, the median OS was 33.2 months; for those with a PSA between 15.08 and ≤46 ng/mL, the median OS was 27.2 months; and for those with a PSA above 46 ng/mL, the median OS was 18.4 months. The hazard ratio for the highest quartile versus the lowest was 3.0 (95% CI, 2.6-3.6).
Eleven baseline characteristics were determined to be significant predictors of OS including: hemoglobin increase, ECOG performance status, age, prior systemic treatment, and more.
Serious adverse events (AEs) were reported in 13.7% of patients and grade 3 to 5 serious AEs were reported in 9.2%. The most common events were disease progression (1.5%), cerebrovascular accident (0.8%), chills (0.7%), syncope (0.6%), and device-related infections (0.5%). Events considered to be possibly related to treatment occurred in 3.9% of patients. Fifty-two patients experienced grade 5 serious AEs and 22 patients died from disease progression.
“Median baseline PSA levels at mCRPC diagnosis have declined steadily since the approval of Provenge in 2010,” said Bruce A. Brown, MD, chief medical officer at Dendreon, in a statement. “Of the nearly 2,000 patients enrolled in PROCEED between 2011-2014 a quarter had a PSA of <5.27 ng/mL, and these men lived much longer than those in the higher quartiles. It’s worth noting that the median baseline PSA levels observed in PROCEED are lower than those in the pivotal IMPACT trial and would likely be lower if PROCEED was enrolling today.”
The investigators noted that the findings were similar to a post-hoc analysis of the phase III IMPACT trial of sipuleucel-T in patients with prostate cancer. The analysis demonstrated that patients with a lower baseline PSA level were associated with a higher OS. Patients with a PSA ≤22.1 ng/mL had a median OS of 41.3 months.3