Pegylated liposomal doxorubicin (Duomeisu®) monotherapy in patients with HER2-negative metastatic breast cancer heavily pretreated with anthracycline and taxanes: a single-arm, phase II study

Breast Cancer Res Treat. 2023 May;199(1):67-79. doi: 10.1007/s10549-023-06894-3. Epub 2023 Mar 6.

Abstract

Purpose: To evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD) in patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) heavily pretreated with anthracycline and taxanes.

Methods: In this single-arm, phase II study, patients with HER2-negative MBC previously treated with anthracycline and taxanes as second- to fifth chemotherapy received PLD (Duomeisu®, generic doxorubicin hydrochloride liposome) 40 mg/m2 every 4 weeks until disease progression, unacceptable toxicity, or completion of six cycles. Primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR), and safety.

Results: Of 44 enrolled patients (median age, 53.5 years; range, 34-69), 41 and 36 were evaluable for safety and efficacy, respectively. In total, 59.1% (26/44) of patients had ≥ 3 metastatic sites, 86.4% (38/44) had visceral disease, and 63.6% (28/44) had liver metastases. Median PFS was 3.7 months (95% confidence interval [CI] 3.3-4.1) and median OS was 15.0 months (95% CI 12.1-17.9). ORR, DCR, and CBR were 16.7%, 63.9%, and 36.1%, respectively. The most common adverse events (AEs) were leukopenia (53.7%), fatigue (46.3%), and neutropenia (41.5%), with no grade 4/5 AEs. The most common grade 3 AEs were neutropenia (7.3%) and fatigue (4.9%). Patients experienced palmar-plantar-erythrodysesthesia (24.4%, 2.4% grade 3), stomatitis (19.5%, 7.3% grade 2), and alopecia (7.3%). One patient displayed a left ventricular ejection fraction decline of 11.4% from baseline after five cycles of PLD therapy.

Conclusion: PLD (Duomeisu®) 40 mg/m2 every 4 weeks was effective and well-tolerated in patients with HER2-negative MBC heavily pretreated with anthracycline and taxanes, revealing a potentially viable treatment option for this population. Trial registration Chinese Clinical Trial Registry: ChiCTR1900022568.

Keywords: Efficacy; HER2-negative; Metastatic breast cancer; Pegylated liposomal doxorubicin; Safety.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Anthracyclines / pharmacology
  • Anthracyclines / therapeutic use
  • Antibiotics, Antineoplastic / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / genetics
  • Doxorubicin / adverse effects
  • Female
  • Humans
  • Middle Aged
  • Neoplasm Metastasis / drug therapy
  • Neutropenia* / drug therapy
  • Polyethylene Glycols / adverse effects
  • Stroke Volume
  • Taxoids / therapeutic use
  • Treatment Outcome
  • Ventricular Function, Left

Substances

  • liposomal doxorubicin
  • Anthracyclines
  • Taxoids
  • Doxorubicin
  • Antibiotics, Antineoplastic
  • Polyethylene Glycols