Phase II randomized trial comparing metronomic anthracycline-containing chemotherapy versus standard schedule in untreated HER2 negative advanced breast cancer: activity and quality of life results of the GOIM 21003 trial

Breast. 2024 Jun:75:103725. doi: 10.1016/j.breast.2024.103725. Epub 2024 Apr 5.

Abstract

Background: Optimizing chemotherapy to achieve disease and symptoms control is a noteworthy purpose in advanced breast cancer (ABC). We reported the activity and quality of life of a phase II study, comparing metronomic regimen with standard schedule as first line chemotherapy for ABC.

Methods: Patients with HER2 negative ABC were randomized to non-pegylated liposomal doxorubicin (NPLD, 60 mg/m2 every 3 weeks) and cyclophosphamide (CTX, 600 mg/m2 every 3 weeks) (Arm A) or NPLD (20 mg/m2 day, on day 1, 8 and 15 every 4 weeks) and metronomic daily oral CTX 50 mg (ARM B). Primary end-points were overall response rate (ORR) and quality of life, secondary progression-free survival (PFS), overall survival (OS) and toxicity.

Results: From August 2012 to December 2017, 121 patients were enrolled, 105 evaluable. Median follow-up was 21.3 months. Most patients had hormone receptor positive. ORR was 43 % in arm A and 50 % in arm B. Median PFS was 8.9 months in arm A and 6,4 months in arm B. There was no difference in OS. Total score was not clinically different between the two arms. Grade 4 neutropenia was observed in 12 patients and 16 patients respectively; alopecia G2 in 41 % (77 %) vs 14 (27 %) in arm A and in arm B respectively. One cardiac toxicity was observed (arm A).

Conclusions: First line metronomic chemotherapy for HER2 negative ABC had similar clinical activity and quite better tolerability than standard schedule and could be considered a further treatment option when chemotherapy is indicated.

Keywords: Anthracyclines; Her2 negative advanced breast cancer; Metronomic chemotherapy.

Publication types

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

MeSH terms

  • Administration, Metronomic*
  • Adult
  • Aged
  • Anthracyclines / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols* / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / pathology
  • Cyclophosphamide* / administration & dosage
  • Doxorubicin* / administration & dosage
  • Doxorubicin* / analogs & derivatives
  • Drug Administration Schedule
  • Female
  • Humans
  • Middle Aged
  • Polyethylene Glycols
  • Progression-Free Survival
  • Quality of Life*
  • Receptor, ErbB-2* / metabolism
  • Treatment Outcome

Substances

  • ERBB2 protein, human
  • liposomal doxorubicin