External validation of a prognostic score for survival in patients with metastatic castration-resistant prostate cancer (CABASCORE) treated with Cabazitaxel.

Lead Investigator: Stéphane Oudard, Assitance Publique des Hôpitaux de Paris
Title of Proposal Research: External validation of a prognostic score for survival in patients with metastatic castration-resistant prostate cancer (CABASCORE) treated with Cabazitaxel.
Vivli Data Request: 9098
Funding Source: None
Potential Conflicts of Interest: Consultancy for and honoraria from: Astellas, Janssen; consultancy for and travel expenses and honoraria from: Bayer, Bristol Myers Squibb, Eisai Merck, Sharp & Dohme, Novartis, and Pfizer; research funding from: Ipsen; consultancy for and research funding and honoraria from: Sanofi.
These conflicts of interest will be declared in any subsequent publication.
Dr. Auclin reports: Travel/accomodation/expenses: Mundipharma; Honoraria (self): Sanofi Genzymes; Consultant: Amgen, Sanofi
These conflicts of interest will be declared in any subsequent publication.

Summary of the Proposed Research:

Prostate cancer is the second most common cancer in male worldwide with more than 1,400,000 new cases in 2020, mainly in highly developped countries. It is also the fifth cause of mortality by cancer in male, worlwide. A great number of prostate cancer are detected at an early stage, leading to complete remissions. Unfortunately, the cancer will relapse and spread in 5 to 10% cases, developping metastases. In addition, 10-15% of all the prostate cancers are initially diagnosed at a metastatic stage. Metastatic prostate cancer treatment rely on different therapy as chemotherapy molecule (a treatment that kills the cancer cells and prevents its growth) and hormonotherapy (the growth of prostate cancer cells are stimulated by hormones. Hormonotherapy is a treatment that blocks the production of theses hormones, therefore blocking the growth of the cancer). Prostate cancer is generally stimulated by male androgenic hormones (a group of sex hormones that stimulate the growth of prostate cancer cells), which is why castration (deprivation of androgenic hormones) is the cornerstone of the metastatic prostate cancer treatment. Nowadays, the combination of the castration therapy with chemotherapy and a new generation of hormonotherapy (that specifically block the androgen receptor [which binds to the androgenic hormones, allowing the body to benefit from its effects. In the prostate cancer, it allows the cancer cells to multiply]) increases the survival of patients with prostate cancer. However, patients will eventually develop a resistance to these type of treatments and especially to the castration therapy. When resistance to castration therapy occurs, other therapies are needed in order to control the disease progression. Several treatments are available in this situation as Cabazitaxel, which is a chemotherapy molecule. It is largely used in mCRPC (metastatic castration-resistant prostate cancer : name given to a prostate cancer that is no more responding to hormonotherapy), given that it improves the survival of the patients. While different treatments are available, clinician’s treatment decision remains uneasy, given that the optimal sequence of treatments is still unknown. Scientific data are needed in order to determined the best therapy sequence in mCRPC.

Therefore, we decided to build a prognostic score, the CABASCORE, aiming to predict the survival of patients under Cabazitaxel regimen in mCRPC patients which could help clinicians to identify patients that are good candidates for such treatment or not.
This CABASCORE was built using clinical, biological and tumor characteristics of patients that were included in the CABASTY clinical trial, which compared two different Cabazitaxel dose regimen in an mCRPC population.
We believe that studying factors that are associated with a better survival is crucial to better identify the patients that will well respond to Cabazitaxel and that developing a prognostic score is a simple and easy-to-use tool for clinicians to deliver its valuable information.

The objective of the present study is to apply the CABASCORE in larger and similar population of patients treated with Cabazitaxel for mCRPC and assess its potential value for treatment decision in this setting.

The design of the study is a retrospective analysis, using patients’ data from different available and independent studies. The CABASCORE will be calculated for each patients using the available data. Then each study populations will be divided in three prognostic groups. Finally, the survival of those groups will be analyzed and compared in order to assess the ability of the CABASCORE to distinguished patients with good, intermidiate and poor response to Cabazitaxel. This method is a widely used and robust approach to validate a prognostic score. The large number of patients from the requested studies will also give statistical power to our analyses.

Requested Studies:

A Randomized, Open Label, Multicenter Study of Cabazitaxel Versus an Androgen Receptor (AR)-Targeted Agent (Abiraterone or Enzalutamide) in mCRPC Patients Previously Treated With Docetaxel and Who Rapidly Failed a Prior AR-targeted Agent (CARD)
Data Contributor: Sanofi
Study ID: NCT02485691
Sponsor ID: LPS14201

Randomized, Open Label Multi-Center Study Comparing Cabazitaxel at 20 mg/m² and at 25 mg/m² Every 3 Weeks in Combination With Prednisone for the Treatment of Metastatic Castration Resistant Prostate Cancer Previously Treated With a Docetaxel-Containing Regimen
Data Contributor: Sanofi
Study ID: NCT01308580
Sponsor ID: EFC11785