Taxane-based Combination Therapies for Metastatic Prostate Cancer

Abstract

Context: Multiple single-agent therapies improving survival are approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC), including two chemotherapies, two androgen-signaling axis-targeting agents, an immunotherapeutic vaccine, and a radiopharmaceutical. Combination therapy can target multiple oncogenic pathways simultaneously, while potentially curbing the development of treatment resistance.

Objective: To provide a succinct overview of taxane-based combination therapies currently being evaluated for the treatment of metastatic prostate cancer.

Evidence acquisition: We searched MEDLINE/PubMed^® and relevant congress databases for literature focused on taxane-based combination therapies being evaluated for the treatment of metastatic prostate cancer. In addition, a systematic search of www.clinicaltrials.gov was performed to gather information regarding ongoing taxane-based combination trials in prostate cancer. This search included phase II or III trials starting after January 1, 2010, which included the terms "docetaxel" or "cabazitaxel" and "prostate", and was then manually filtered for combination studies.

Evidence synthesis: Single-agent therapy yields modest increments in survival. The success of combining docetaxel with androgen deprivation to improve overall survival (OS) for metastatic hormone-sensitive disease suggests the potential of similar approaches in mCRPC. Several classes of biological drugs have previously been combined with docetaxel for mCRPC in clinical trials without improvement in OS. However, combining docetaxel or cabazitaxel with newer agents with established single-agent benefit, such as radium-223, second-generation androgen pathway-targeted agents, or other chemotherapies, has the potential to benefit patients when compared with taxane chemotherapy alone. Our search revealed that the majority of trials currently assessing taxanes are focused on combination therapies: a combination approach is being evaluated in 37 of 47 trials assessing docetaxel and in 18 of 34 trials assessing cabazitaxel.

Conclusions: Despite prior failures, novel taxane-based combination therapies have the potential to improve outcomes in mCRPC. Challenges include the absence of validated predictive biomarkers for the selection of suitable patients and the potential for enhanced toxicity.

Patient summary: Patients with metastatic prostate cancer have access to multiple therapies improving survival. Many advanced epithelial cancers are treated with combinations of drugs; however, prostate cancer has remained an exception. A number of clinical studies have shown that combining chemotherapy with other classes of therapy may improve patient outcomes in prostate cancer. Here, we summarize the various combinations that are tested in the clinic and review the results.

Keywords: Chemotherapy; Combination therapy; Metastatic prostate cancer.