CDK4/6 inhibitors show broad benefit in HR+/HER2- metastatic breast cancer

  • Lancet Oncol

  • 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

  • A US Food and Drug Administration (FDA)− pooled analysis of 7 trials of 3 cyclin-dependent kinase 4/6 (CDK4/6) inhibitors (CDKIs; palbociclib, ribociclib, and abemaciclib) finds broad-based PFS benefit across all subgroups of patients with hormone receptor (HR)-positive HER2-negative advanced or metastatic breast cancer (mBCa).

Why this matters

  • This is the first comprehensive pooled analysis of efficacy in patient subgroups, including less common ones, of 3 CDKIs approved by FDA and the European Medicines Agency (EMA).

Study design

  • Pooled analysis of 7 trials (n=4200) of 3 CDKIs or placebo plus an aromatase inhibitor (letrozole or anastrozole) or fulvestrant.
  • Primary outcome: PFS.
  • Funding: None.

Key results

  • Median follow-up, 19.7 months.
  • CDKI plus endocrine therapy bested placebo plus endocrine therapy across all trials.
    • Difference in estimated median PFS: 8.8 (range: 6.8-13.3) months.
    • HR, 0.59 (95% CI, 0.54-0.64).
  • CDKI plus endocrine therapy groups had better PFS in all prespecified clinicopathological subgroups, including:
    • In first-line aromatase inhibitor-treated patients:
      • PFS difference, 13.1 months. 
      • HR, 0.55 (95% CI, 0.49-0.62).
    • In first-line fulvestrant-treated patients:
      • PFS difference not estimable. 
      • 0.58 (0.42-0.80).
    • In fulvestrant-treated patients in the second-line setting:
      • PFS difference, 6.9 months. 
      • 0.56 (0.49-0.64).

Limitations

  • Varying granularity of analysis across trials did not allow for analysis of some subgroups.