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

PURPOSE: This multicenter, single-arm, phase II 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 (1,000 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. The median age was 64 years, 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% confidence interval (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 wild-type 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, were feasible, safe, and efficacious in patients with high-volume mCSPC and warrant further study in larger randomized trials.