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.
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Introduction
Breast cancer has become the most commonly diagnosed cancer globally in 2020, surpassing lung cancer (11.4%), with an estimated 2,261,419 new cases (11.7%), and the fourth leading cause (6.9%) of cancer-related deaths worldwide, with an estimated 684,996 new deaths in 2020 [1]. Approximately 20–50% of patients with early breast cancer will eventually develop metastatic disease [2], and 5–10% of patients are initially diagnosed with metastatic disease [3]. Among patients with metastatic breast cancer (MBC), 62% are diagnosed with human epidermal growth factor receptor 2 (HER2)-negative disease [4]. Despite considerable advances in new treatments, MBC remains treatable but incurable, with the goal of treatment to prolong patients’ survival and improve their quality of life [5, 6].
During the past 70 years, the highest number of new drugs for breast cancer was approved [7]. Nevertheless, conventional anthracyclines (doxorubicin and epirubicin) and taxanes remain the cornerstones of breast cancer therapy regardless of the molecular subtype, whether in the neoadjuvant/adjuvant setting or metastatic setting[6, 8,39, 43].
This study had several limitations. First, this study had a single-center, open-label design with no control arm. Second, the implementation of the study took longer than originally planned. The slow enrollment of patients was aggravated by the COVID-19 pandemic. Third, this was an exploratory trial with small sample sizes.
Conclusion
In summary, our study demonstrated that PLD (Duomeisu®) monotherapy at 40 mg/m2 every 4 weeks was effective and safe in patients with HER2-negative MBC heavily pretreated with conventional anthracycline and taxanes, indicating that this treatment is a viable treatment option for this population.
Data availability
The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.
Abbreviations
- ADC:
-
Antibody–drug conjugate
- AE:
-
Adverse event
- AIDS:
-
Acquired immune deficiency syndrome
- CBR:
-
Clinical benefit rate
- CI:
-
Confidence interval
- CR:
-
Complete response
- DCR:
-
Disease control rate
- HER2:
-
Human epidermal growth factor receptor 2
- HR:
-
Hormone receptor
- LVEF:
-
Left ventricular ejection fraction
- MBC:
-
Metastatic breast cancer
- ORR:
-
Objective response rates
- OS:
-
Overall survival
- PFS:
-
Progression-free survival
- PLD:
-
Pegylated liposomal doxorubicin
- PPE:
-
Palmar-plantar erythrodysesthesia
- PR:
-
Partial response
- RECIST:
-
Response Evaluation Criteria for Solid Tumor
- SD:
-
Stable disease
- SG:
-
Sacituzumab govitecan
- T-DXd:
-
Trastuzumab deruxtecan
- Trop-2:
-
Trophoblast cell surface antigen-2
- ULN:
-
Upper limit of normal
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Acknowledgements
We thank the participating patients and their families for their contributions to the study. We also thank Joe Barber Jr., PhD., from Liwen Bianji (Edanz) (www.liwenbianji.cn) for editing the English text of a draft of this manuscript. This research was designed and led by the study investigators. Shijiazhuang Pharmaceutical Group Ouyi Pharmaceutical Co. Ltd (CSPC) provided some part of the study drug for this trial.
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HJ and HL contributed to the study conception and design. All authors were involved in the acquisition of data. The first draft of the manuscript was written by HJ, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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HPL received some part of the study drug for this trial from Shijiazhuang Pharmaceutical Group Ouyi Pharmaceutical Co. Ltd. All other authors declare that they have no potential conflicts of interest to disclose.
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Jiang, H., Li, H., Song, G. et al. 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 199, 67–79 (2023). https://doi.org/10.1007/s10549-023-06894-3
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DOI: https://doi.org/10.1007/s10549-023-06894-3