Can baseline or Ra-223-induced changes in the plasma predict progressive disease mCRPC patients?

Abstract

Purpose or Objective Bone targeting agents such as Radium-223 (Ra-223) have changed the landscape for managing metastatic castration-resistant prostate cancer (mCRPC). Ra-223 is approved for men with symptomatic bone metastases but no known visceral metastases. Not all patients respond to Ra-223, thus early stratification of patients can aid personalisation of treatment plans. Our study aimed to explore the feasibility of measuring baseline and early Ra-223 induced changes in circulating cytokines, chemokines and growth factors involved in the immune response. Materials and Methods Fifty patients with mCRPC with bone disease were recruited into the CAPRA study and received up to six four weekly injections of Ra-223 (Figure 1). Patients were labelled responders (R) or non-responders (NR) depending on whether they had improvement or progression of symptoms. Plasma was isolated from whole blood immediately after collection, then frozen and stored at -80oC. Using a 30-plex Luminex assay, a technology that detects fluorescence (MFI) to estimate the concentration of protein, we identified plasma-based cytokines, chemokines and growth factors and compared the levels between Ra-223 responders and non-responders. Results Analysis of the first seven patients in our pilot cohort at baseline (T1) and after the first three injections of Ra-223 (T4) suggests that there are differences between baseline levels of some cytokines, with higher expression of the immune stimulating cytokine; IL-12 observed in the responders (n = 4) versus non-responders (n = 3) (MFI:189.8±33 vs. 79.5±13 respectively) (Figure 2). In addition, the pilot data suggests that there is an increase in the immunosuppressive cytokine, IL-6 in the non-responders (n = 2) after treatment with Ra-223 (T1 vs. T4: 34.8±3 vs. 43.9±8) and a decrease in IL-6 in the responders (n = 4) (T1 vs. T4: 47.9±8 vs. 42.5±8) after treatment with Ra-223 Our pilot data demonstrates the feasibility of using a multiplexed assay to measure differences in baseline and Ra-223- induced changes in circulating markers in non-responders and responders. Further study is worthwhile to explore whether these circulating markers can predict response to Ra-223.