CASCARA Phase II Tests Cabazitaxel-Carboplatin-Abiraterone In mCSPC

Key Takeaways

• Twelve-month PSA progression-free survival was 84.6%, and 12-month overall survival was 94.8%.
• Complete PSA and objective responses were reported, while HRR-mutated patients had numerically fewer complete PSA responses and shorter progression-free survival than HRR wild-type patients.
• Fatigue, nausea, and diarrhea were common, and the authors described the regimen as feasible, safe, and efficacious and as warranting larger randomized evaluation.

Men with high-volume metastatic castration-sensitive prostate cancer treated with cabazitaxel-carboplatin induction followed by abiraterone plus continuous ADT had 12-month PSA progression-free survival of 84.6%. The CASCARA phase II study evaluated this sequence in a multicenter, single-arm phase II trial, moving from chemotherapy intensification to hormonal maintenance within the same first-line strategy. Treatment began with cabazitaxel and carboplatin before maintenance abiraterone, with androgen deprivation therapy continued throughout. The regimen was assessed in men with high-volume disease early in systemic treatment.

Eligible participants had high-volume mCSPC and no more than 3 months of prior ADT, and 61 men enrolled across eight sites. Patients received six 21-day cycles of cabazitaxel 20 mg/m2 plus carboplatin AUC 4 with continuous ADT. Maintenance then used abiraterone 1,000 mg daily plus prednisone 5 mg daily, and the primary endpoint was freedom from PSA or radiographic progression at 12 months. Baseline disease burden was substantial, with median age 64 years and median PSA 6.6 ng/mL at study entry. Most participants had Gleason grade group 5 disease or at least 10 metastases, placing the cohort in a distinctly high-risk group.

Secondary endpoints included complete PSA response, objective response, progression-free survival, and safety, and overall survival was also reported in the abstract. Complete PSA response occurred in 66.7% of participants, and complete objective response occurred in 30.7%. Investigators also reported 12-month overall survival of 94.8%, with a 95% confidence interval of 84.7% to 98.3%. The primary endpoint focused on control of PSA or radiographic progression at 12 months. The reported outcomes spanned progression control, PSA decline, radiographic response depth, and 12-month survival.

Homologous recombination repair mutations were present in 19.6% of participants, and this exploratory subgroup had fewer complete PSA responses than HRR wild-type patients. The corresponding complete PSA response rates were 33.3% and 70.3%, and progression-free survival was poorer with a hazard ratio of 2.43. The 95% confidence interval for that hazard ratio was 0.93 to 6.39, and investigators noted that the direction was contrary to their hypothesis. Common side effects included fatigue, nausea, and diarrhea, and the authors described the regimen as feasible, safe, and efficacious and as warranting study in larger randomized trials. These exploratory findings added a cautious biomarker signal to the overall results.