Satraplatin (S) demonstrates significant clinical benefits for the treatment of patients with HRPC: Results of a randomized phase III trial

Abstract

5019 Background: Chemotherapeutic options for HRPC are limited. S is a novel oral platinum compound. Methods: The SPARC trial is a multinational randomized double blind study comparing S 80 mg/m2/day x 5 q5weeks po + prednisone (P) vs placebo + P in HRPC patients (pts) who failed prior chemotherapy. In this analysis, progression-free survival (PFS) was the primary endpoint, defined as a composite endpoint of radiologic progression, symptomatic progression, skeletal events or death. All cases were blindly adjudicated for progression by an independent review committee (IRC). Results: 950 pts were accrued between Sept 2004 and Jan 2006. Baseline characteristics were well balanced between treatment arms. 51% of the pts had received prior docetaxel. 68% were ≥ 65 yrs old and 27% were ≥ 75 yrs old. Pts received a median of 4 courses in the S arm (range:1–28) vs 2 courses in the placebo arm (range 1–16). 802 pts had an IRC defined progression-free (PFS) event consisting in 80% of the cases of radiologic progression, pain progression or death. All analyses were conducted on an intent-to-treat basis. S was associated with a 31% reduction in the risk of PFS events (HR=0.69; 95% CI: 0.60–0.80; p<0.00001) and a 33% reduction in the risk of pain progression (HR=0.67; 95% CI: 0.54 - 0.83; p=0.00028). Consistent results in favor of S were found for PFS and time to pain progression in all subsets examined, including pts treated with prior docetaxel. Superior PSA response (25% vs.12%, p=0.00007), objective tumor response (7% vs. 1%, p<0.002), pain response (24% vs. 14%, p<0.005), and duration of pain response (HR=0.59; 95%CI: 0.35–1.00; p=0.049) were observed for S. Final analysis of overall survival awaits the occurrence of the pre-specified number of events. S was generally well tolerated - myelosuppression was the most frequent side effect, but grade 4 neutropenia was uncommon (4%) and a single patient had grade 4 thrombocytopenia. Grade 3/4 non-hematologic side effects included infection (4%), vomiting (2%) and diarrhea (2%). Conclusions: S is well tolerated and significantly reduces the risk of disease progression for HRPC pts who have failed prior chemotherapy. Supported by GPC Biotech and Pharmion No significant financial relationships to disclose.

Final analysis of a phase II trial using sorafenib for metastatic castration‐resistant prostate cancer

“…Of the 24 patients, 21 (88%) in the second stage had received previous chemotherapy with docetaxel, compared to only 12 of 22 (55%) in stage 1. Most patients (17) were ECOG status 1.…”

“…Second-line treatment after docetaxel failure has been studied using several agents, including mitoxantrone [14], ixabepilone [15], carboplatin [16] and satraplatin [17], with a reported median OS using these agents of 9.8-17 months. The median OS for sorafenib was 18.3 months in the present study, comparable to other second-line cytotoxic regimens.…”

Second‐line therapy for castrate‐resistant prostate cancer: A literature review

“…The Satraplatin and Prednisone Against Hormone Refractory Prostate Cancer (SPARC) phase III trial examined the effectiveness of satraplatin in patients with progressive metastatic CRPC after one prior chemotherapy regimen (Table 2). 41,42 Crossover to the satraplatin arm from the placebo arm at progression was not permitted. The study accrued 950 patients over a period of 28 months.…”

Role of targeted therapy in the treatment of advanced prostate cancer

“…The demonstration that chemotherapy can, indeed, improve survival in this patient population and to an extent similar to that seen in other chemotherapy‐sensitive tumour types has refuted the notion that CRPC is chemotherapy refractory and reinvigorated efforts to develop more effective chemotherapy regimens and determine the best agents to use as second‐line therapy. Several agents have been investigated in the second‐line setting, including satraplatin, mitoxantrone, vinorelbine, ixabepilone, and patupilone (Table 1) [44–50].…”