Treatment with the immunotherapy Provenge (sipuleucel-T) in a real-world setting is showing  similar safety and efficacy in men with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC) as in clinical trials, a study shows.

The observational registry study — called PROCEED (NCT01306890) — conducted at urology and medical oncology clinics showed that men with lower prostate specific antigen (PSA) levels at baseline lived nearly four years after receiving Provenge.

“The median survival of four years following treatment with PROVENGE is meaningful,” Celestia S. Higano, MD, FACP, lead author of the PROCEED analysis, said in a press release.

The study, “Real-world outcomes of sipuleucel‐T treatment in PROCEED, a prospective registry of men with metastatic castration‐resistant prostate cancer,” was published in the journal Cancer.

Provenge, marketed by Dendreon Pharmaceuticals, is an immunotherapy that uses a patient’s own immune cells to fight prostate cancer. In it, a fraction of white blood cells that have been exposed to a prostate cancer protein are primed to activate the remaining immune cells to fight cancer.

In 2010, Provenge became the first immunotherapy approved for metastatic prostate cancer in the United States after it significantly extended patients’ lives by four months in the IMPACT Phase 3 trial (NCT00065442).

Since then, and because prostate cancer management is rapidly changing, researchers designed PROCEED to study the safety and efficacy of mCRPC treatment protocols involving Provenge in a real-world setting.

PROCEED enrolled 1,976 mCRPC patients across 140 community clinics and 52 academic sites. Patients were very similar to those included in IMPACT, with a somewhat worse performance status, and a slightly higher Gleason score (a measure of cancer aggressiveness).

However, in PROCEED, some patients (78%) were also treated with additional anticancer agents, including androgen receptor inhibitors, chemotherapies, and radiotherapy, not yet approved at the time of IMPACT.

Also, patients in PROCEED had much lower PSA levels (15.0 ng/mL) than those in IMPACT (51.7 ng/mL), likely because patients are being diagnosed earlier.

During a follow-up period of 46.6 months (3.8 years), 1,255 patients died, 964 (76.8%) because of cancer progression.

Overall, patients died of prostate cancer a median of 42.7 months from their first Provenge injection, but patients with lower PSA levels (5.27 ng/mL or lower) at baseline lived the longest — 47.7 months.

In contrast, median prostate cancer survival was 33.2 months for patients whose PSA levels were between 5.27 and 15.08 ng/mL, 27.2 months for those with levels between 15.08 and 46 ng/mL, and 18.4 months for those with the highest levels (above 46 ng/mL).

“PROCEED provides a real-world portrait of the expected [overall survival] after sipuleucel-T in mCRPC patients in the modern era of five additional life-prolonging agents,” said Higano, who is also a professor in the Division of Medical Oncology, Department of Medicine, University of Washington School of Medicine and Fred Hutchinson Cancer Research Center.

Researchers also noted that approximately one-third of the participants (32.5%) had not received any additional therapy to prolong survival 1 year after Provenge, and 17.4% at 2 years. Also, most of these patients (95%) had Provenge as first-line mCRPC therapy as recommended by the National Comprehensive Cancer Network (NCCN).

“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. “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.”

Regarding safety, the incidence of serious adverse events “in PROCEED was low and was comparable to that documented during IMPACT,” researchers stated. The rates of cardiovascular events were also low (3.5%), which is important for this patient population with multiple comorbidities.