Metastatic breast cancer: dual bests single blockade of HER2 in updated ALTERNATIVE

  • Johnston SRD & al.
  • J Clin Oncol
  • 21 Aug 2020

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

  • Dual blockade of HER2 protein with lapatinib (LAP) plus trastuzumab (TRAS) prolongs PFS compared with single blockade with TRAS in patients with HER2+ metastatic breast cancer.
  • Both groups also received aromatase inhibitor (AI) according to updated results of phase 3 ALTERNATIVE trial.

Why this matters

  • Dual HER2 blockade provides a safe and effective chemo-sparing option for HER2+ metastatic breast cancer.

Study design

  • Phase 3 randomized controlled trial (N=355) comparing LAP (oral 1000 mg/day)+TRAS (6 mg/kg intravenous maintenance dose every 3 weeks)+AI (investigator choice) vs TRAS+AI in patients with HER2+ metastatic breast cancer.
  • Funding: GlaxoSmithKline; Novartis; others.

Key results

  • The dual-blockade group had longer PFS than the single-blockade group:
    • Median PFS, 11 vs 5.6 months.
    • HR, 0.62 (P=.0063).
  • Dual blockade also yielded significantly better OS:
    • Median, 46 vs 40.0 months with single blockade.
    • HR, 0.60 (95% CI, 0.35-1.04).
  • Serious adverse events were similar between groups.
  • The dual-blockade group had fewer discontinuations.

Limitations

  • Open-label design.