Relationship of sipuleucel-T with time to first use of opioid analgesics (TFOA) in patients (pts) with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC) on the IMPACT trial.

Abstract

74 Background: Sipuleucel-T (sip-T) is an autologous cellular immunotherapy which was shown to prolong survival in pts with mCRPC in the pivotal IMPACT trial (NCT00065442) (Kantoff PW et al. N Engl J Med 2010;363:411-22). TFOA was a prespecified secondary end point but was subsequently removed as an end point following a protocol amendment to expand enrollment to include minimally symptomatic pts in addition to asymptomatic pts. TFOA data were nevertheless collected in the 512 pts enrolled in the trial. Methods: At baseline, pts were required to have an average pain score <4 on a 10-point visual analog scale and no ongoing opioid analgesic use (OAU). Concomitant medications were collected until confirmed objective disease progression. OAU was identified by medical review of preferred drug names in the coded concomitant medication information on case report forms (CRFs). OAU unrelated to cancer pain (e.g. meperidine used for infusion reactions) was excluded by medical review of CRFs. Pts not reporting OAU were censored at the time of protocol amendment. TFOA was analyzed using a Cox regression model with adjustment for baseline PSA and LDH. Results: 341 sip-T- and 171 placebo-treated patients were evaluated. Median TFOA was 11.9 months (mo) with sip-T vs 8.3 mo for placebo (hazard ratio=0.727; 95% confidence interval 0.536, 0.987; p=0.041). Censoring rate was high (sip-T, 66.9%; placebo, 61.4%). Median follow-up for OAU was 5.2 mo (sip-T, 5.3 mo; placebo, 5.0 mo). Kaplan-Meier estimates of being opioid free at 12 mo were 48.7% for sip-T vs 39.7% for placebo; curve separation began at 6 mo. Significant independent baseline predictors of shorter TFOA were: higher PSA, alkaline phosphatase; younger age; higher number of bone metastases; Gleason score ≥8; ECOG performance status 1; higher weight; and prior primary radiotherapy. Conclusions: Relative to placebo, sip-T delays the TFOA in patients with asymptomatic or minimally symptomatic mCRPC. Clinical trial information: NCT00065442.