Samarium-153-EDTMP (Quadramet(®)) with or without vaccine in metastatic castration-resistant prostate cancer: A randomized Phase 2 trial

PSA-TRICOM is a therapeutic vaccine in late stage clinical testing in metastatic castration-resistant prostate cancer (mCRPC). Samarium-153-ethylene diamine tetramethylene phosphonate (Sm-153-EDTMP; Quadramet(®)), a radiopharmaceutical, binds osteoblastic bone lesions and emits beta particles causing local tumor cell destruction. Preclinically, Sm-153-EDTMP alters tumor cell phenotype facilitating immune-mediated killing. This phase 2 multi-center trial randomized patients to Sm-153-EDTMP alone or with PSA-TRICOM vaccine. Eligibility required mCRPC, bone metastases, prior docetaxel and no visceral disease. The primary endpoint was the proportion of patients without radiographic disease progression at 4 months. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and immune responses. Forty-four patients enrolled. Eighteen and 21 patients were evaluable for the primary endpoint in Sm-153-EDTMP alone and combination arms, respectively. There was no statistical difference in the primary endpoint, with two of 18 (11.1%) and five of 21 (23.8%) in Sm-153-EDTMP alone and combination arms, respectively, having stable disease at approximately the 4-month evaluation time point (P = 0.27). Median PFS was 1.7 vs. 3.7 months in the Sm-153-EDTMP alone and combination arms (P = 0.041, HR = 0.51, P = 0.046). No patient in the Sm-153-EDTMP alone arm achieved prostate-specific antigen (PSA) decline > 30% compared with four patients (of 21) in the combination arm, including three with PSA decline > 50%. Toxicities were similar between arms and related to number of Sm-153-EDTMP doses administered. These results provide the rationale for clinical evaluation of new radiopharmaceuticals, such as Ra-223, in combination with PSA-TRICOM.