KEY TAKEAWAYS
- The phase I/II trial aimed to evaluate the final results of ORR, rPFS, and OS.
- The ORR and rPFS were calculated using the Clopper-Pearson Exact Method, and the OS was calculated using the Kaplan-Meier method.
- The study concluded that the combination of ENZ+CAB showed favorable OS and rPFS compared to other trials. Cross-trial comparisons are discouraged due to confounders.
The phase I/II trial of Enzalutamide (ENZ) + cabazitaxel (CAB) in metastatic castration-resistant prostate cancer (mCRPC) without prior chemotherapy showed promising efficacy and safety. ENZ and CAB were well-tolerated, and 80% of patients had PSA decline ≥50%. Researchers evaluated the final outcome of objective response rate(ORR), radiographic progression-free survival (rPFS), and overall survival (OS).
The study used the Clopper-Pearson Exact Method to calculate the ORR (CR/PR) and 95% confidence intervals (CI). Response assessment followed RECIST 1.1 for measurable disease and Prostate Cancer Working Group 2 criteria for non-measurable (bone) disease. Kaplan-Meier method estimated median rPFS and OS with 95% CI (data cutoff: 6/1/22). Statistical analysis was performed using R: A language and environment for statistical computing.
Out of 37 patients, 35 were included in the efficacy analysis (1 withdrew consent, 1 lost to follow-up), 20% had prior chemotherapy exposure for mHSPC, and 25% had prior abiraterone (ABI) exposure, including 25.7% with both chemotherapy and ABI history. About 28 patients were evaluable for ORR based on at least one on-study imaging. The median follow-up was 23.7 months. Median OS was 25.1 months (95% CI 19.4 – 37.6). Median PSA PFS was 11.9 months (95% CI 9.2 – 15.4), and median rPFS was 22.2 months (95% CI 13.6 – 25.2). PK assessments showed ENZ decreased CAB levels significantly (P<0.05): CAB (monotherapy) Cmax 178.9 ng*h/ml vs CAB (in the presence of ENZ) Cmax 85.5 ng*h/ml. The study found that the ENZ+CAB combination therapy showed promise in mCRPC with longer OS and rPFS than in single-agent CAB trials. Caution in cross-trial comparisons and further research on chemo-hormonal therapies and biomarkers in mCRPC is needed.
Source: https://meetings.asco.org/abstracts-presentations/227186
Clinical Trial: https://www.clinicaltrials.gov/study/NCT02522715
Alexandra Sokolova, Julie N. Graff, Claire E Smith, Tomasz M. Beer, Emile Latour, Petros Grivas, Michael Thomas Schweizer, Celestia S. Higano, Joshi J. Alumkal, Jacqueline Vuky, Evan Y. Yu, and Heather H. Cheng. Journal of Clinical Oncology (2023) 41:16_suppl, 5047-5047.
