CHAARTED2: Cabazitaxel Plus Abiraterone After Initial Docetaxel for mCRPC

The addition of cabazitaxel to abiraterone/prednisone significantly prolongs progression-free survival (PFS) in patients with metastatic castration-resistant prostate cancer (mCRPC) who previously received chemohormonal therapy (androgen deprivation therapy [ADT] plus docetaxel) for hormone-sensitive prostate cancer (HSPC) compared with abiraterone/prednisone alone, according to new research.

These results from the CHAARTED2 trial of the Eastern Cooperative Oncology Group (ECOG)-ACRIN Cancer Research Group was presented by Christos Kyriakopoulos, MD, of the University of Wisconsin Carbone Cancer Center, as a late-breaking abstract at the 2024 American Society of Clinical Oncology Annual Meeting.

Initial results of CHAARTED demonstrated a significant survival benefit from early treatment with ADT plus docetaxel in patients with high-volume metastatic HSPC. However, most patients are likely to develop CRPC and will require additional treatment.

Dr. Kyriakopoulos and colleagues hypothesized that additional treatment with chemohormonal therapy in the CRPC setting would improve outcomes for these patients. The CHAARTED2 trial, then, was a prospective, open-label, phase 2 trial including 223 patients with mCRPC who were previously treated with ADT plus docetaxel for HSPC. They were randomized (1:1) to received either abiraterone/prednisone plus cabazitaxel (25 mg/m² for up to 6 cycles; n=111) or abiraterone/prednisone alone (n=112). Patients were stratified based on ECOG performance status of 0 versus 1/2, time from initiation of ADT to development of CRPC of less than 12 months versus greater than 12 months, and presence versus absence of visceral metastases.

The primary end point of CHAARTED2 was PFS, defined as time from randomization to radiographic progression, symptomatic deterioration requiring discontinuation of treatment, or death. Among the secondary end points were time to PSA progression (TTPP), overall survival (OS), and safety.

After a median follow-up of 47.3 months, Dr. Kyriakopoulos and colleagues found that the median PFS was longer for patients in the cabazitaxel plus abiraterone/prednisone arm versus the abiraterone/prednisone alone arm (14.9 months vs 9.9 months, respectively). Notably, the increased PFS was more prominent in patients aged less than 65 years (15.6 months vs 9.8 months; P=.08), ECOG performance status of 0 (20.9 months vs 10.1 months; P=.01), time to CRPC of less than 12 months (12.9 months vs 5.1 months; P=.006), and absence of visceral metastases (18.1 months vs 10.1 months; P=.01).

Researchers also reported that the median TTPP was longer in the combination versus monotherapy arm (10.0 months vs 6.1 months, respectively; P=.002). However, no difference in OS was observed between the treatment arms in the interim analysis (25.0 months vs 26.9 months, respectively; P=.67).

Furthermore, they acknowledged that more grade 3 or higher treatment-related adverse events were noted in patients receiving the combination treatment, which was expected.