Adding carboplatin to cabazitaxel ups PFS in aggressive variant CRPC

  • Corn PG & et al.
  • Lancet Oncol
  • 9 Sep 2019

  • curated by Deepa Koli
  • Univadis Clinical Summaries
Access to the full content of this site is available only to registered healthcare professionals. Access to the full content of this site is available only to registered healthcare professionals.

Takeaway

  • 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.

Study design

  • 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.

Key results

  • 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.

Limitations

  • Open-label design.