(UroToday.com) 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. In clinical practice, many patients with prostate cancer often receive sequential androgen-signaling-targeted inhibitors. Patients who have progressed on an androgen-signaling-targeted inhibitor may not respond to a second alternative androgen-signaling-targeted inhibitor, possibly due to shared resistance mechanisms.
The CARD trial demonstrated the superiority of cabazitaxel over abiraterone or enzalutamide in patients with mCRPC who had previously received docetaxel and progressed ≤ 12 months on the alternative androgen receptor-targeted agent.1 Real-world studies offer the possibility of validating the results of large, randomized trials, such as CARD, by including more varied patient populations and helping to identify trends in healthcare service utilization. At the 2020 virtual European Society of Medical Oncology – (ESMO), annual meeting, Dr. Ronald de Wit and colleagues presented the results of their evaluation of a large real-world dataset comparing characteristics of patients receiving cabazitaxel after docetaxel and one androgen-signaling-targeted inhibitor with the CARD-eligible population.
Real-world data were collected from Medimix LiveTrackerTM, a retrospective, global oncology database of healthcare professional-reported electronic patient medical forms, which was used to identify patients with mCRPC who received cabazitaxel and prior docetaxel and abiraterone or enzalutamide (in any order), between 2001 and 2019. Only patients with available cabazitaxel treatment duration were included. Patients were included from France, Germany, Italy, Spain, UK, USA, Japan, and Brazil.
In total, 452 patients were included in the real-world evidence cohort. The median age was similar to the CARD trial (73 vs 70 years), however, Eastern Cooperative Oncology Group performance status score ≥ 2 was greater in the real-world evidence cohort (45% vs 4.7%). More patients in the real-world evidence cohort versus CARD received prior androgen-signaling-targeted inhibitors before docetaxel (48% vs 39%; abiraterone 57% vs 43%; enzalutamide 43% vs 56%) and had prior androgen-signaling-targeted inhibitor treatment duration > 12 months (30% vs 17%). Patients in the real-world evidence cohort had more aggressive disease features versus CARD: M1 at diagnosis (46% vs 38%) and Gleason 8–10 (65% vs 57%), although the proportion of patients with visceral metastases (12% vs 16%) was comparable with CARD. The most frequent treatment sequences in the CARD-like cohort included docetaxel as the first treatment in the sequence of 52% of patients and androgen-signaling-targeted inhibitors as the first for 48% of patients:
Despite more patients in the real-world evidence cohort vs CARD receiving the lower cabazitaxel dose (20 mg/m2 dose; 55% vs 21%), cabazitaxel treatment duration in the real-world evidence cohort was comparable with CARD (21.9 vs 22.0 weeks):
Dr. de Wit concluded his presentation of the real-world evidence of CARD-like patients with the following summary points:
- This real-world data analysis demonstrated that in the clinical setting, more patients receive both abiraterone and enzalutamide before receiving cabazitaxel despite evidence suggesting that abiraterone and enzalutamide may share mechanisms of resistance
- In the CARD-like cohort, despite more patients having poorer ECOG performance status, more aggressive disease features, and a larger proportion of patients receiving a lower dose of cabazitaxel, the duration of cabazitaxel received was similar to that reported in the CARD study
- More patients in the CARD-like cohort received prior androgen-signaling-targeted inhibitor treatment for a duration greater than 12 months compared with the CARD study for both arms
- In the real world, it is likely that patients are treated beyond progression for the first androgen-signaling-targeted inhibitor since current standard of practice is to continue abiraterone or enzalutamide after rising PSA until other assessments have confirmed progression
- These findings show that, in the recent past, sequential use of androgen-signaling-targeted inhibitors is still frequent and that the CARD population is reflective of patients in routine clinical practice
1. de Wit R, de Bono J, Sternberg CN, et al. Cabazitaxel versus Abiraterone or Enzalutamide in Metastatic Prostate Cancer. N Engl J Med 2019 Dec 26;381(26):2506-2518.
Presented by: Ronald de Wit, MD, PhD, Department of Medical Oncology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Written by: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, Twitter: @zklaassen_md at the European Society for Medical Oncology Virtual Congress, ESMO Virtual Congress 2020 #ESMO20, 18 Sept – 21 Sept 2020
ESMO Virtual Congress 2020: Cabazitaxel Activity in Men with Metastatic Castration-Resistant Prostate Cancer with and without DNA Damage Repair Defects
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
CARD Study Demonstrates Cabazitaxel Improves Pain and Health-Related Quality of Life Analysis in Patients with mCRPC – Karim Fizazi
Cabazitaxel versus Abiraterone or Enzalutamide in Metastatic Prostate Cancer – Beyond the Abstract