Dr Kyriakopoulos on Adding Cabazitaxel to Abiraterone/Prednisone in Patients With MCRPC

Christos Kyriakopoulos, MD, of the University of Wisconsin Carbone Cancer Center, presents findings from the CHAARTED2 trial (NCT03419234), which evaluated the efficacy of adding cabazitaxel (Jevtana) to abiraterone (Zytiga)/prednisone (Rayos) in patients with metastatic castration-resistant prostate cancer who had previously been treated with androgen deprivation therapy (ADT) and docetaxel for hormone-sensitive prostate cancer.

The study enrolled 223 patients with metastatic castration-resistant prostate cancer, randomly assigning them to receive either cabazitaxel plus abiraterone/prednisone (n = 111) or abiraterone/prednisone alone (n = 112). The primary endpoint was progression-free survival (PFS), with secondary endpoints including time to PSA progression, overall survival (OS), and safety. Stratification factors included ECOG performance status, time from initiation of ADT to development of castration-resistant prostate cancer, and presence of visceral metastases.

Kyriakopoulos emphasized that the addition of cabazitaxel to standard abiraterone therapy significantly prolonged PFS by five months compared to abiraterone alone (14.9 months vs. 9.9 months, P = 0.049; HR 0.73).

This improvement is clinically significant, especially for patients with aggressive disease who historically have the poorest outcomes. The combination therapy also improved PSA kinetics, including higher PSA response rates and longer time to PSA progression (10 months vs. 6.1 months, P = 0.002).

However, despite these benefits, the study did not show a statistically significant improvement in overall survival (25.0 months vs. 26.9 months, P = 0.67).Kyriakopoulos noted that the study was underpowered for this endpoint and that patients had access to other life-prolonging therapies upon progression on abiraterone, which may have influenced the results.

The combination therapy resulted in more grade ≥3 adverse events, as expected with cabazitaxel treatment. These included increased rates of neutropenia, febrile neutropenia, and gastrointestinal toxicities.

The increased adverse events highlights the need for careful patient selection and management when considering this combination therapy, explained Kyriakopoulos.