Sipuleucel-T Treatment Effects Persist Even in Radiation-Treated Patients

SAN FRANCISCO—Real-world data demonstrates that prior radiation therapy may no longer be a barrier for successful immunotherapy with sipuleucel-T in patients with metastatic castration-resistant prostate cancer (mCRPC), according to research presented at the 2014 Genitourinary Cancers Symposium.

Sipuleucel-T—an autologuous cellular immunotherapy indicated for patients with asymptomatic or minimally symptomatic mCRPC)—was approved by the US Food and Drug Administration based largely on the results of the randomized, controlled, phase 3 Immunotherapy for Prostate Adenocarcinoma Treatments (IMPACT) study. In the IMPACT population, patients receiving sipuleucel-T experienced a 22% reduction in the risk of death, but this analysis excluded all mCRPC patients who had already undergone radiation therapy—given the high probability that these patients had suppressed bone marrow function and, subsequently, decreased immune function.

1 - Steven E. Finkelstein, MDSteven E. Finkelstein, MD, from 21st Century Oncology Translational Research Consortium in Scottsdale, Arizona, led an investigation of the Registry of Sipuleucel-T Therapy in Men With Advanced Prostate Cancer (PROCEED), looking specifically at patients who had undergone radiation therapy prior to taking sipuleucel-T. Unlike IMPACT, PROCEED patients who received palliative radiation for bone pain prior to starting sipuleucel-T were not excluded from the study population—which allowed investigators to evaluate the effects of prior radiation on sipuleucel-T manufacturing parameters.

In the current analysis, patients treated with sipuleucel-T ≤6 months were eligible for inclusion. In addition to baseline demographics and patient information, Finkelstein et al. assessed the following product parameters: total nucleated cell (TNC) count, antigen presenting cell (APC) count (determined by CD54+ cell count), and APC activation (determined by upregulation of CD54—a measure of product potency). 

Of the 1,244 patients who completed therapy, 112 (9.0%) patients had received palliative radiation for bone metastases prior to immunotherapy with sipuleucel-T and 517 (41.6%) patients had no prior radiation of any kind.  To limit the comparison of non–radiation-treated patients to those who had palliative radiation, patients with radical prostatectomy were isolated from each group for further study—resulting in 44 patients in the palliative radiation group and 159 in the non–radiation-treated group.

While median cumulative APC counts were similar between each group, TNC counts and degree of APC activation were lower in the palliative radiation group (TABLE). However, the percentage of patients receiving all three infusions in each group was comparable (palliative radiation = 93.2%; non–radiation-treated = 95.0%).

Palliative radiation patients

Non–radiation-treated patients

p Value

TNC counts

9.89 per unit

12.09 per unit

0.002

APC activation

34.2

38.5

0.048

Ultimately, Dr. Finkelstein and colleagues concluded that, although TNC counts and APC activation were lower in radiation-treated patients, “In the real-world setting, there is no evidence that prior radiation inhibits successful production of sipuleucel-T.” They also noted that effects on in vivo post-treatment immune measures are being collected prospectively in a companion trial (PRIME).

Source: Finkelstein SE, Nordquist LT, Dakhil SR, et al. Impact of prior radiation treatment (tx) on sipuleucel-T (sip-T) product parameters in PROCEED patients (pts). Abstract presented at 2014 Genitourinary Cancers Symposium; San Francisco California. January 30, 2014.