Breast cancer CNS metastases: new lapatinib strategy allows high doses

  • Morikawa A & al.
  • Clin Cancer Res
  • 15 Apr 2019

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

  • An alternating dosing strategy of 2 central nervous system (CNS)-penetrant chemotherapy agents, lapatinib and capecitabine, allows escalating doses of lapatinib to reach 1500 mg twice daily (BID) as the maximum tolerated dose (MTD) for treating CNS metastases in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBCa).

Why this matters

  • Lapatinib, a tyrosine kinase inhibitor, and capecitabine have shown preclinical and clinical antitumor efficacy in CNS metastases, but dose-limiting toxicity prevents antitumor response.
  • Escalating doses of lapatinib by alternation with fixed-dose capecitabine has potential efficacy against CNS mets.
  • Findings in this phase 1 trial warrant progression to phase 2.

Study design

  • Phase 1 trial (n=11) of escalating doses of lapatinib (starting at 1000 mg BID) on days 1-3 and days 15-17 and capecitabine (1500 mg BID) on days 8-14 and days 22-28 of every 28-day cycle.
  • Funding: Novartis; NIH; others.

Key results

  • 36% of 11 patients had brain only mets, 45% leptomeningeal mets, and 18% intramedullary spinal cord mets.
  • Lapatinib obtained an MTD of 1500 mg BID.
  • 3 patients tolerated therapy for >6 months, 2 of them for >1 year.
  • Most common treatment-emergent toxicities: grade 1/2 diarrhea, grade 2 vomiting.
  • Antitumor activity in CNS and non-CNS was seen in 2 patients.

Limitations

  • Lack of control group.

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