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CARD Trial: Cabazitaxel versus Abiraterone or Enzalutamide in Metastatic Prostate Cancer

Curated by Clinicians: Educational Forum with Videos, Abstracts and Conference Information
Videos
Therapy Resistance Identified in Circulating Tumor Cell Morphologic Sub-Types Present Prior to Treatment in the CARD Trial - Cora Sternberg
Real-World Evidence For Patients with mCRPC Treated with Cabazitaxel - Ronald de Wit
Cabazitaxel is Active in Men with mCRPC with DDR Alterations - Karim Fizazi and Mihaela Aldea
Evaluating Circulating Tumor Cells in Patients on the CARD Trial - Eleni Efstathiou
NCCN Guidelines Updated for Prostate Cancer M1 Systemic Therapy Based Upon The CARD Trial - Tanya Dorff
Cabazitaxel versus Abiraterone or Enzalutamide in Metastatic Castration-Resistant Prostate Cancer - Karim Fizazi
Journal Club: Discussing Quality of Life in Patients with Metastatic Prostate Cancer Following Treatment with Cabazitaxel Versus Abiraterone or Enzalutamide - Christopher Wallis & Zachary Klaassen
Effect of Cabazitaxel vs Abiraterone or Enzalutamide on Patient-Reported Outcomes in mCRPC: A Pre-Planned EQ-5D-5L Analysis of the CARD Study - Neal Shore
Cabazitaxel Demonstrates Improved Overall Survival when Compared to an Alternative AR-targeted Agent (CARD) - Cora Sternberg
The Clinical Implications of The Efficacy and Safety in Older Patients with Metastatic Castration-Resistant Prostate Cancer Receiving Cabazitaxel versus Abiraterone or Enzalutamide In The CARD Trial - William Oh and Stephen Freedland
The Clinical Implications and Health-related Quality of Life Benefits: Reviewing the CARD Study Results in Men with mCRPC - Neal Shore
CARD Study Demonstrates Cabazitaxel Improves Pain and Health-Related Quality of Life Analysis in Patients with mCRPC - Karim Fizazi
Clinical Implications of the CARD Trial - Cora Sternberg
Cabazitaxel is a New Standard of Care for Third Line Metastatic Prostate Cancer - Bertrand Tombal
Publications
Articles and Abstracts

Cabazitaxel was shown to improve overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) after abiraterone/enzalutamine and docetaxel failure, though benefit by the presence of DNA damage repair (DDR) defects is unknown.

Despite treatment advances in prostate cancer, it is associated with approximately 79,000 deaths in Europe and 34,000 deaths in the USA each year, presenting a clear unmet need.1,2 Most patients with metastatic castration-resistant prostate cancer (mCRPC) are ≥ 70 years of age and the median age of those who die from the disease is 80 years.3,4

There is growing evidence that a high neutrophil-to-lymphocyte ratio (NLR) is associated with poor overall survival (OS) for patients with metastatic castration-resistant prostate cancer (mCRPC). In the CARD study (NCT02485691), cabazitaxel significantly improved radiographic progression-free survival (rPFS) and OS versus abiraterone or enzalutamide in patients with mCRPC previously treated with docetaxel and the alternative androgen-receptor-targeted agent (ARTA).

In the CARD study (NCT02485691), cabazitaxel significantly improved median radiographic progression-free survival (rPFS) and overall survival (OS) versus abiraterone/enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) who had previously received docetaxel and progressed ≤12 mo on the alternative agent (abiraterone/enzalutamide).

Treatment for poor prognosis metastatic castration-resistant prostate cancer (mCRPC) includes taxane chemotherapy and androgen receptor pathway inhibitors (ARPI). We sought to determine optimal treatment in this setting.

In the CARD study (NCT02485691), cabazitaxel significantly improved clinical outcomes versus abiraterone or enzalutamide in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel and the alternative androgen-signalling-targeted inhibitor.

In the CARD study, cabazitaxel significantly improved radiographic progression-free survival and overall survival versus abiraterone or enzalutamide in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel and the alternative androgen signalling-targeted inhibitor.

As medical oncologists, urologists, radiation oncologists, and other clinicians, we find ourselves feeling very comfortable understanding Kaplan Meier survival curves and forest plots describing subgroups in the setting of different treatments. We review CTCAE adverse event data, drilling down on the 10% of adverse effects that happen most commonly, and nearly always arrive at the conclusion that “such and such treatment is relatively well tolerated”.

The robust outcome of CARD with a hazard ratio (HR) for radiographic progression-free survival (rPFS) 0.54 in favor of cabazitaxel allows meaningful subgroup analyses. Preplanned subgroups of particular interest and that, importantly, retained statistical significance including the time to failure on the first androgen receptor targeted agents (ARTA) (0-6 months, 6-12 months) and the docetaxel- first ARTA sequence.

The efficacy and safety of cabazitaxel, as compared with an androgen-signaling-targeted inhibitor (abiraterone or enzalutamide), in patients with metastatic castration-resistant prostate cancer who were previously treated with docetaxel and had progression within 12 months while receiving the alternative inhibitor (abiraterone or enzalutamide) are unclear.

Conference Coverage
Conference Highlights Written by Physician-Scientist
Presented by Johann S. de Bono, MD, MSc, PhD, FRCP, FMedSci
The ESMO 2021 virtual annual meeting’s prostate cancer session included a presentation by Dr. Johann de Bono presenting data assessing the impact of circulating tumor cell (CTC) morphologic sub-types prior to treatment in the CARD trial.1 
Presented by Alicia Morgans, MD, MPH
In the on-demand poster session of the ESMO Annual Congress, Dr. Alicia Morgans discussed a modeling analysis of cabazitaxel compared to repeat treatment with an androgen receptor targeting agent (ARTA) among patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel and the alternative ARTA.
Presented by Johann de Bono, MB ChB FRCP MSc Ph.D. FMedSci.
There have been many advances in the field of systemic therapy for advanced prostate cancer in the past 15 years. While, prior to the publication of TAX-327, there were no available treatments with proven life-prolonging benefits, we now have many treatments available with demonstrable improvements in overall survival.
Presented by Cedric Pobel, MD
The field of advanced prostate cancer has rapidly progressed over the past 15 years. Prior to the publication of TAX-327, there were no proven life-prolonging therapies for patients with metastatic castration-resistant prostate cancer (mCRPC). Dr. Pobel and colleagues assess the feasibility and efficacy of cabazitaxel multiple rechallenges in patients with mCRPC.
Presented by Casilda Llacer Perez, MD
The CARD trial was a randomized open-label study of cabazitaxel versus the alternative anti-androgen therapy in patients with metastatic castration resistant prostate cancer (mCRPC) who had progressed on docetaxel and also progressed on either enzalutamide or abiraterone within 12 months of therapy initiation.
Presented by Ronald de Wit, MD, PhD
Taxanes (docetaxel, cabazitaxel) and androgen-signaling-targeted inhibitors (abiraterone, enzalutamide) have shown survival benefits in metastatic castration resistant  prostate cancer (mCRPC), however until recently the optimal sequence of these treatments was unclear.
Presented by Ronald De Wit PhD
(UroToday.com) It is well known that inflammation is a hallmark of cancer, harboring a critical role in tumor development and metastatic progression in many cancers, including prostate cancer.
Presented by Mihaela Aldea, MD, PhD
Up to 30% of metastatic castration-resistant prostate cancer (mCRPC) men harbor DNA damage repair defects and may benefit from poly-ADP ribose polymerase (PARP) inhibitors after abiraterone/enzalutamide and docetaxel failure. Cabazitaxel was recently shown to improve overall survival in this population
Presented by Gero Kramer, MD
 The CARD study was a multicenter, randomized, open-label study enrolling patients with metastatic castrate-resistant prostate cancer who progressed in less than 12 months on prior androgen receptor-targeted agent1 (before or after docetaxel therapy).
Presented by Bertrand F. Tombal, MD, PhD
The CARD trial, initially presented at ESMO 2019 and subsequently published, addressed the question of appropriate third line therapy in mCRPC for patients who had previously received docetaxel and also progressed on an anti-androgen therapy (either abiraterone or enzalutamide) within 12 months.
Presented by Cora N. Sternberg, MD, FACP
Prostate cancer is the 2nd and 3rd leading cause of cancer death in the USA and in Europe, respectively,1,2 with most deaths occurring in men over the age of 75. In men with metastatic castrate-resistant prostate cancer (mCRPC), there are multiple treatment options available today,
Presented by Karim Fizazi, MD, PhD
San Francisco, California (UroToday.com) The survival outcomes of the CARD trial, a practice-informing study of men with pre-treated metastatic castration-resistant prostate cancer (mCRPC), have previously been reported.
Presented by Silke Gillessen, MD
Barcelona, Spain (UroToday.com) Dr. De Wit’s presentation of the positive CARD trial, Dr. Silke Gillessen provided an invited discussion regarding the implications and practice-changing measures that result from these findings.
Presented by Ronald De Wit, MD, PhD
Barcelona, Spain (UroToday.com) Multiple therapeutic options have been approved for the treatment of men with metastatic castration-resistant prostate cancer (mCRPC), including the second-generation anti-androgens abiraterone and enzalutamide, and chemotherapy with docetaxel or cabazitaxel.
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