Ribociclib+letrozole downstages high-risk HR+ early breast cancer in phase 2

  • Prat A & al.
  • Lancet Oncol
  • 1 Jan 2020

  • curated by Miriam Davis, PhD
  • Univadis Clinical Summaries
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Takeaway

  • Ribociclib (CDK4/6 inhibitor) plus letrozole (endocrine therapy) achieves molecular downstaging of hormone receptor (HR)-positive, HER2-negative, luminal B early breast cancer (eBCa), according to results of the phase 2 CORALLEEN trial.

Why this matters

  • Findings suggest that ribociclib+letrozole may enable a chemotherapy-free strategy for high-risk eBCa.

Study design

  • Phase 2 multicenter (21 hospitals in Spain), randomized controlled trial in HR+/HER2− eBCa patients with luminal B tumors with mostly high-risk-of-relapse (ROR) (n=106).
  • Randomization was to ribociclib (oral 600 mg/day for 3 weeks on, 1 week off) plus letrozole daily oral 2.5 mg vs chemotherapy with 4 cycles of doxorubicin (intravenous [IV] 60 mg/m2) and cyclophosphamide (IV 600 mg/m2 every 21 days) followed by weekly paclitaxel (IV 80 mg/m2) for 12 weeks.
  • Primary outcome: % achieving low ROR by PAM50 molecular profiling test.
  • Funding: Novartis; others.

Key results

  • Baseline characteristics:
    • Ribociclib group: 85% high ROR, 15% intermediate ROR.
    • Chemo group: 89% high ROR, 11% intermediate ROR.
    • Both groups had 0% low ROR.
  • At median follow-up of 200 days:
    • Ribociclib: 22.5% high ROR, 30.6% intermediate ROR, 46.9% low ROR.
    • Chemo group: 21.2% high ROR, 30.8% intermediate ROR, 46.1% low ROR.
  • Conversion to luminal A subtype:
    • Ribociclib group: 87.8% (95% CI, 75.3%-95.4%);  vs
    • Chemo group: 82.7% (95% CI, 69.7%-91.8%).

Limitations

  • Open-label design.