Pyrotinib combined with metronomic etoposide in heavily pretreated HER2-positive metastatic breast cancer: a single-arm, phase II study

BMC Cancer. 2024 Oct 18;24(1):1290. doi: 10.1186/s12885-024-13041-8.

Abstract

Background: Exploration of novel combination mode of pyrotinib and chemotherapy for heavily pretreated HER2-positive metastatic breast cancer (MBC) and how to balance survival benefits and compliance are still urgent problems in clinical practice. The current single-arm prospective phase II study aimed to evaluate the efficacy and safety of pyrotinib in combination with metronomic oral etoposide in heavily pretreated HER2-positive MBC.

Methods: HER2-positive MBC patients previously treated with trastuzumab were enrolled to receive oral pyrotinib 400 mg per day and metronomic oral etoposide 50 mg per day d1-21 every 28 days, until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). The secondary endpoints were objective response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR), overall survival (OS), and safety.

Results: 22 patients were enrolled with a median of 4 prior treatment regimens for MBC. During the follow-up of 20 evaluable patients, the median PFS was 9.0 months (95% CI, 7.6-10.4 months), and the median OS was 27.0 months (95%CI, 20.9-33.1 months). The ORR was 30% (6/20), the DCR was 80% (16/20), and the CBR was 65% (13/20). The most common grade 3 adverse events (AEs) included nausea (15%), vomiting (15%), diarrhea (5%), anemia (5%), and peripheral neuropathy (5%). No grade 4 or lethal AEs were observed.

Conclusion: The combination of pyrotinib with metronomic oral etoposide has achieved promising clinical benefits in heavily pretreated HER2-positive MBC, with acceptable and manageable toxicity.

Trial registration: Registry number: NCT03923179. Registered April 18, 2019.

Keywords: Etoposide; HER2-positive; Metastatic breast cancer; Metronomic chemotherapy; Pyrotinib.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Acrylamides* / administration & dosage
  • Acrylamides* / adverse effects
  • Acrylamides* / therapeutic use
  • Administration, Metronomic*
  • Adult
  • Aged
  • Aminoquinolines
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / mortality
  • Breast Neoplasms* / pathology
  • Etoposide* / administration & dosage
  • Etoposide* / adverse effects
  • Etoposide* / therapeutic use
  • Female
  • Humans
  • Middle Aged
  • Progression-Free Survival
  • Prospective Studies
  • Receptor, ErbB-2* / metabolism

Substances

  • pyrotinib
  • Etoposide
  • Receptor, ErbB-2
  • Acrylamides
  • ERBB2 protein, human
  • Aminoquinolines

Associated data

  • ClinicalTrials.gov/NCT03923179