- Adding carboplatin to cabazitaxel is safe and associated with improved PFS among men with metastatic castration-resistant prostate cancer (mCRPC), particularly those with aggressive variant prostate carcinoma (AVPC).
- AVPC was identified using molecular criteria, a signature with defects in ≥2 of TP53, RB1, and PTEN.
Why this matters
- Phase 3 evaluation is warranted.
- Phase 1: 9 patients with progressive mCRPC received cabazitaxel.
- Phase 2: 160 patients with progressive mCRPC were randomly assigned to cabazitaxel±carboplatin.
- Funding: Sanofi Genzyme; others.
- Phase 1 showed no dose-limiting toxicities; grade 3 events included anemia, fatigue, thrombocytopenia, hypomagnesemia, diarrhea. The maximum tolerated dose was 25 mg/m2.
- Median follow-up in phase 2 was 31.0 months.
- Cabazitaxel+carboplatin significantly improved median PFS (7.3 vs 4.5 months; HR, 0.69; P=.018), but not OS (P=.50).
- AVCP: longer median PFS (6.0 vs 2.2 months, P=.00033) and OS (17.4 vs 9.9 months, P=.0024).
- No AVCP: no PFS (P=.74) or OS (P=.19) advantage.
- Cabazitaxel+carboplatin was more likely to yield a >50% decline in PSA (OR, 2.53; P=.016) or bone-specific alkaline phosphatase (OR, 3.92; P=.0033).
- Grade 3-5 toxicities were higher with combination therapy, most commonly fatigue (20% vs 9%) and anemia (23% vs 4%).
- No treatment-related deaths reported.
- Open-label design.