High-dose chemo for breast cancer: 20-year follow-up finds complex legacy

  • JAMA Oncol

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

  • A 20-year follow-up of high-dose chemotherapy (HDCT) for breast cancer with ≥4 positive lymph nodes shows no OS benefit except for a subgroup with ≥10 nodes.
  • No benefit seen with triple-negative breast cancer (TNBC).
  • This phase 3 trial compared HDCT+autologous hematopoietic stem cell transplant with conventional-dose chemotherapy (CDCT).

Why this matters

  • This is the largest such randomized controlled trial, with the longest follow-up.

Study design

  • 20-year follow-up of Dutch trial of 885 patients age 
  • 4 cycles of chemo at same dose as CDCT, but fifth cycle in HDCT group contained cyclophosphamide, 6000 mg/m2; thiotepa, 480 mg/m2; and carboplatin, 1600 mg/m2; followed by hematopoietic stem cell transplant.
  • Funding: None disclosed.

Key results

  • No OS increase with HDCT:
    • 41.5% CDCT vs 45.3% HDCT. 
    • HR: 0.89 (95% CI, 0.75-1.06).
  • Subgroup with ≥10 ALN had absolute improvement of 14.6%.
    • HR, 0.72 (95% CI, 0.54-0.95).
  • Subgroup with TNBC had nonsignificant absolute improvement of 15.4%.
    • HR: 0.67 (95% CI, 0.42-1.05).
  • No differences between groups in second malignant neoplasm or major cardiovascular event.
  • HDCT group had more hypertension, hypercholesterolemia, and dysrhythmias.

Limitations

  • Currently used CDCT differs from version in this trial.