Breast cancer brain mets: high-dose intravenous methotrexate shows promise in French study

  • Bazan F & al.
  • BMC Cancer
  • 1 Nov 2019

  • curated by Miriam Davis, PhD
  • 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

  • High-dose intravenous methotrexate (MTX), which crosses the blood-brain barrier, shows a favorable efficacy and toxicity profile in a small, uncontrolled phase 2 trial of patients with central nervous system (CNS) metastatic breast cancer (mBCa).

Why this matters

  • Brain metastasis accounts for 10%-42% of mBCa.
  • Standard of care, consisting of radiotherapy and surgery, only carries a median survival of
  • Results of this trial are promising enough to warrant a trial with even higher-dose MTX.

Study design

  • Phase 2 open-label, uncontrolled trial of single-group, high-dose intravenous MTX (3 g/m2) given to consecutive patients with CNS mBCa (n=22) seen at a university hospital in France (2004-2009).
  • Time to progression (TTP) is the interval from first treatment and date of progressive disease or death.
  • Funding: None.

Key results

  • Patient composition: 50% hormone receptor (HR)-positive, 45% HR-negative, 9% triple-negative.
  • Median follow-up, 11 months.
  • CNS response to MTX:
    • 9% partial response.
    • 45% disease stabilization.
    • 45% disease progression.
  • Response to MTX at other metastatic sites: 
    • 39% disease stabilization.
    • 61% disease progression.
  • TTP: 2.1 (95% CI, 1.4-2.9) months.
  • OS: 6.3 (95% CI, 1.8-10) months.
  • Toxicity:
    • No grade 5 toxicity.
    • 18% had grade 3-4 hematological toxicity.
    • Most common grade 3-4 nonhematological toxicities were serum hepatic transaminases (18%) and stomatitis (9%).

Limitations

  • Single-center, open-label, uncontrolled observational design.
  • Small sample size.