ER+ metastatic breast cancer: dasatinib plus letrozole show promise in phase 2 trial

  • Paul D & al.
  • NPJ Breast Cancer
  • 1 Jan 2019

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

  • The Src kinase inhibitor dasatinib shows promise in combination with letrozole by increasing the clinical benefit rate (CBR), according to a phase 2 noncomparative trial in patients with estrogen receptor (ER)-positive human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer.

Why this matters

  • Dasatinib may work by preventing acquired resistance to aromatase inhibitor (AI) therapy, which is associated with higher mortality.

Study design

  • Noncomparative, parallel-group, phase 2 trial (n=120) of dasatinib (100 mg/day orally) plus letrozole (2.5 mg/day orally) vs letrozole alone; patients with disease progression on letrozole alone were allowed to crossover to dasatinib+letrozole.
  • CBR was defined as complete response+partial response+stable disease ≥6 months.
  • Funding: Bristol-Myers Squibb.

Key results

  • Letrozole+dasatinib had a higher CBR than projected (71% [95% CI, 58%-83%] vs projected CBR of the combination, 56%).
  • Letrozole alone had a higher CBR than projected (66% [95% CI, 52%-77%] vs projected CBR of 39%).
    • In the crossover group (n=35), the CBR was 23% with a median PFS of 3.7 months.
  • Letrozole+dasatinib had a median PFS of 20.1 months vs 9.9 months on letrozole alone.
  • Letrozole+dasatinib had a median OS of 48.6 months vs 41.9 months on letrozole alone.

Limitations

  • Noncomparative design.
  • No placebo in combination with letrozole.