SWOG S0354: A phase II trial of CNTO328, a monoclonal antibody against interleukin-6 (IL-6), in chemotherapy pretreated patients (pts) with castration- resistant prostate cancer (CRPC)

5143 Background: IL-6 facilitates cancer cell survival via pleiotrophic effects on proliferation, apoptosis, angiogenesis, differentiation, and chemo-resistance. A multicenter phase II study of CNTO328 in chemo pretreated CRPC pts was conducted. Methods: Eligible pts had one prior chemotherapy, Zubrod performance status 0–2, and adequate end-organ function. Regimen: CNTO328 6 mg/kg IV q2 weeks x 12 cycles. Response assessment was q6 weeks. Primary endpoint was PSA response rate (RR) defined as ≥50% reduction. Accrual was completed in 2 stages, with planned accrual of 20 eligible pts in the first stage and 40 overall. Plasma cytokines were measured by Luminex in 44 pts. Results: Of 62 pts, 54 were eligible; all had received prior taxane therapy. Two (3.7%; 95% CI: 0.5%, 12.8%) had PSA response. Of 47 pts evaluable by RECIST, none had a response and 10 (21%) had stable disease (SD). With median follow-up of 6.6 months, median progression-free survival is 1.6 months (95% CI: 1.6, 1.7). Grade 4 toxicity included 1 case of DIC and 1 CNS ischemia; grade 3 toxicities included elevated AST (1), gastritis/esophagitis (2), thrombocytopenia (2), pain (2), leucopenia (1), and neuropathy (2). Median baseline IL-6 levels were 12.5 pg/mL (IQR: 2.5, 41.5). Pts with levels >12.5 pg/mL had worse 6-month survival vs. < 12.5 pg/mL (53% vs 94%, p = 0.02). Post-cycle 1, IL-6 levels were > 250-fold higher, indicating antibody-target complex formation. 33/39 pts had a decline in C-reactive protein (CRP) plasma levels at 6 weeks. Conclusions: CNTO328 was well-tolerated and resulted in a PSA RR of 3.7% and RECIST SD rate of 21%. Declining CRP levels during treatment reflect biologic activity. Elevated baseline IL-6 levels portend a poor prognosis. Additional translational studies will be presented. Additional study of CNTO328 in combination may be warranted. [Table: see text]