|The following article features coverage from the 2020 Genitourinary Cancers Symposium meeting. Click here to read more of Renal and Urology News’ conference coverage.|
SAN FRANCISCO—Sipuleucel-T combined with radium-223 was associated with a lower peripheral immune response but improved clinical outcomes compared with sipuleucel-T alone among men with metastatic castration-resistant prostate cancer (mCRPC) enrolled in a phase 2 clinical trial, investigators reported at the 2020 Genitourinary Cancers Symposium.
In the trial, a team led by Catherine Handy Marshall, MD, MPH, of the Johns Hopkins University School of Medicine in Baltimore, randomly assigned 32 men to receive either sipuleucel-T plus radium-223 or sipuleucel-T alone. Each treatment arm had 16 men. In both groups, 69% of men had Gleason score 8 to 10 cancer.
All patients had asymptomatic mCRPC with bone predominant metastases and no visceral metastases greater than 1 cm. Men in the combination arm received sipuleucel-T between the second and third dose of radium-223. The primary endpoint was T-cell proliferation in peripheral blood in response to the PA2024 antigen.
Sipuleucel-T is an autologous cell-based immunotherapy that is FDA approved for treating asymptomatic or minimally symptomatic mCRPC. Radium-223 is an alpha-emitting radioisotope and bone-seeking calcium mimetic. It selectively targets areas with increased bone turnover. Radium-223 is FDA approved for use in the treatment of mCRPC with symptomatic bone metastases. It is thought that radioactive agents cause tumors to produce more antigen, which would enhance the immune modulation induced by sipuleucel-T and thus improve clinical outcomes.
Clinical endpoints were radiographic or clinical PFS, PSA response (50% or greater decline), and alkaline phosphatase response (30% or greater decline). Patients had a median follow-up of 5.3 months (range 2.8 to 26.6 months.
At week 6, the change from baseline in the PA2024 proliferation index was 25.3% in the monotherapy arm compared with 7% in the combination arm. Although the T-cell response was less in the combination than monotherapy arm, median progression-free survival (PFS) was longer in the combination arm (9.3 vs 3.1 months), Dr Handy Marshall and her colleagues reported. Combination therapy was associated with a 74% reduced risk of progression compared with monotherapy. In addition, 33% and 60% of the combination-therapy arm had PSA responses and alkaline phosphatase responses, respectively, compared with 0% and 7% of the monotherapy arm, respectively. All of these between-group differences were statistically significant.
“Since neither agent reliably induces PSA responses alone, these data suggest a synergistic effect of the combination,” the authors wrote in their poster.
The investigators reported no safety concerns with the combination therapy.
Disclosure: Research funding from Bayer/Dendreon Pharmaceuticals
Read more of our coverage of the 2020 Genitourinary Cancers Symposium by visiting the conference page.
Marshall CH, Park JC, DeWeese TL, et al. Randomized phase II study of sipuleucel-T (SipT) with or without radium-223 (Ra223) in men with asymptomatic bone-metastatic castrate-resistant prostate cancer (mCRPC). Presented at the 2020 Genitourinary Cancers Symposium held February 13 to 15 in San Francisco. Abstract 130.