Carboplatin, Cabazitaxel and Abiraterone in High-Volume Metastatic Castration-Sensitive Prostate Cancer: The CASCARA Phase 2 Study

Abstract Purpose: This multi-center single-arm phase 2 trial evaluated the safety and efficacy of cabazitaxel and carboplatin followed by abiraterone, plus androgen deprivation therapy (ADT), in patients with high-volume metastatic castration-sensitive prostate cancer (mCSPC). Patients and Methods: Eligible patients had high-volume mCSPC and ≤3 months of prior ADT. Patients received six 21-day cycles of cabazitaxel (20 mg/m²) and carboplatin (AUC 4) with continuous ADT, followed by maintenance abiraterone (1000 mg daily) and prednisone (5 mg daily). The primary endpoint was the proportion of patients free of prostate-specific antigen (PSA) or radiographic progression at 12 months. Secondary endpoints included complete PSA response (≤0.2 ng/mL), objective response, progression-free survival (PFS), and safety. Overall survival (OS) was also reported. Results: Sixty-one participants were enrolled at eight sites. Median age was 64, median baseline PSA was 6.6 ng/mL (0.07-745.7 ng/mL), 73.3% had Gleason grade group 5, 69.5% had 10 or more metastases, and 19.6% had a homologous recombination repair (HRR) mutation. PSA-PFS at 12 months was 84.6% (95%CI, 72.5-91.7%), and OS at 12 months was 94.8% (84.7-98.3%). Complete PSA response was 66.7%, and complete objective response was 30.7%. Contrary to our hypothesis, relative to HRR-wildtype patients, HRR-mutated patients (19.6%) had numerically fewer complete PSA responses (33.3% vs 70.3%) and inferior PFS (HR 2.43, 95%CI 0.93-6.39). Common side effects of this quadruplet regimen included fatigue, nausea, and diarrhea. Conclusions: Cabazitaxel and carboplatin followed by abiraterone, together with ADT, was feasible, safe, and efficacious in patients with high-volume mCSPC, and warrants further study in larger randomized trials.