Patients received RAM + docetaxel or placebo + docetaxel on day 1 of a 21-day cycle until discontinuation criteria were met. Population pharmacokinetic analyses predicted RAM minimum concentrations after the first dose. Multivariate and matched case control analyses were performed to evaluate the exposure-response and overall survival relationship.
Poor prognostic factors were more frequent in the lower exposure quartiles suggesting a possible disease-pharmacokinetic interaction. Higher exposure quartiles were associated with longer survival and smaller hazard ratios compared to placebo. Limitations of the study include small sample size, limited time point, disease-pharmacokinetic interaction which may be confounding.
The RAM + docetaxel quartile with the highest exposure and more favorable prognostic features had better overall survival and objective response rates. There was an observed disease-pharmacokinetic interaction (for example from weight loss, inflammation, liver toxicity) that may impact exposure-response results and warrants further investigation.
Presented by: Ronald De Wit, MD, PhD, Erasmus MC Cancer Institute in Rotterdam, The Netherlands
Written by: Selma Masic, MD, Urologic Oncology Fellow (SUO), Fox Chase Cancer Center, Philadelphia, PA. Twitter:@selmasic at the 2019 American Society of Clinical Oncology Genitourinary Cancers Symposium, (ASCO GU) #GU19, February 14-16, 2019 - San Francisco, CA