Single-agent metronomic versus weekly oral vinorelbine as first-line chemotherapy in patients with HR-positive/HER2-negative advanced breast cancer: The randomized Tempo Breast study

Breast. 2024 Apr:74:103681. doi: 10.1016/j.breast.2024.103681. Epub 2024 Feb 9.

Abstract

Introduction: Single-agent oral vinorelbine is a standard of care for hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC) that has progressed on endocrine therapy. Metronomic administration may offer a better balance of efficacy and safety than standard regimens, but data from previous trials are scarce.

Methods: In this open-label, multicenter, phase II trial, patients were randomized to oral vinorelbine administered on a metronomic (50 mg three times weekly) or weekly (60 mg/m2 in cycle 1, increasing to 80 mg/m2 if well tolerated) schedule. Treatment was continued until disease progression or intolerance. The primary endpoint was disease control rate (DCR, the proportion of patients with a best overall confirmed response of CR, PR, or stable disease lasting 6 months or more).

Results: One-hundred sixty-three patients were randomized and treated. The DCR was 63.4% (95% confidence interval [CI]: 52.0-73.8) with metronomic vinorelbine and 72.8% (95% CI: 61.8-82.1) with weekly vinorelbine. Weekly vinorelbine was also associated with longer progression-free survival (5.6 vs 4.0 months) and overall survival (26.7 vs 22.3 months) than metronomic vinorelbine, but was associated with more adverse events.

Conclusions: In this randomized phase II trial, single-agent metronomic oral vinorelbine was effective and well tolerated as first-line chemotherapy for patients with HR-positive/HER2-negative ABC. Formal comparisons are not done in this phase II study and one can simply observe that confidence intervals of all endpoints overlap. When deciding for a chemotherapy after failure of endocrine therapy and CDK 4/6 inhibitors, oral vinorelbine might be an option to be given with either schedule.

Clinical trial registration number: EudraCT 2014-003860-19.

Keywords: Administration; Chemotherapy; Disease control rate; HR+/HER2-advanced breast cancer; Metronomic; Oral; Vinorelbine; Weekly administration.

Publication types

  • Randomized Controlled Trial
  • Multicenter Study
  • Clinical Trial, Phase II

MeSH terms

  • Administration, Metronomic
  • Antineoplastic Combined Chemotherapy Protocols
  • Breast / metabolism
  • Breast Neoplasms*
  • Female
  • Humans
  • Progression-Free Survival
  • Receptor, ErbB-2 / metabolism
  • Treatment Outcome
  • Vinblastine
  • Vinorelbine

Substances

  • Vinorelbine
  • Receptor, ErbB-2
  • Vinblastine