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Efficacy and Safety of Neoadjuvant Treatment with Bevacizumab, Liposomal Doxorubicin, Cyclophosphamide and Paclitaxel Combination in Locally/Regionally Advanced, HER2-Negative, Grade III at Premenopausal Status Breast Cancer: A Phase II Study

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Abstract

Background

In the era of personalized therapy, targeted treatment in specific patient populations is mandated.

Objective

We evaluated the efficacy and safety of neoadjuvant treatment on locally advanced breast cancer (LABC) with a monoclonal agent against vascular endothelial growth factor (VEGF), bevacizumab plus chemotherapy combination of liposomal doxorubicin, cyclophosphamide and paclitaxel (PLAC-B).

Methods

Patients enrolled were at premenopausal status and characterized by human epidermal growth factor receptor 2 (HER2)-negative, hormone-receptor positive (estrogen receptor/progesterone receptor-positive [ER/PR+]) or triple-negative (TNBC), LABC (T > 3 cm), with high-grade ductal carcinoma. Patients had to have a measurable disease and Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, with adequate hematologic, renal, and hepatic function. Patients received intravenous liposomal doxorubicin 30 mg/m2, cyclophosphamide 600 mg/m2, paclitaxel 120 mg/m2, and bevacizumab 8 mg/kg on day 1 of 15-day cycles for four cycles (four administrations as neoadjuvant treatment). The primary endpoint was complete clinical (cCR) and pathologic (pCR) response rates, while secondary endpoints included safety, breast-conserving surgery (BCS) conversion rate, and disease-free survival (DFS).

Results

Sixty-two women were enrolled; 20 were ER/PR+ and 42 had TNBC. All underwent surgery, six received mastectomy, and 56 (90.3%) received BCS, with an equal conversion rate from initial indication for mastectomy. cCR was 25.8%. pCR in the breast and axilla occurred in 24 patients (38.7%). pCR was 42.9% for TNBC and 30% for ER/PR+. Hematologic adverse events (AEs) included neutropenia (74.2% total; 22.6% grade 3 [G3]) and febrile neutropenia (6.5% G3); non-hematologic G3 AEs included nausea (6.5%), mucositis (9.7%), and infection (3.2%), all of which were managed without negative sequelae. Over a 3-year follow-up, all patients were alive and DFS was 87.1%.

Conclusion

PLAC-B as neoadjuvant treatment of this subpopulation with TNBC and ER/PR+ patients is effective and safe. Further studies are necessitated.

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Author notes

  1. Ekaterini C. Tampaki, Athanasios Tampakis, and Constantinos E. Alifiers made equal contributions into the drafting of this manuscript.

Authors and Affiliations

  1. Second Department Propaedeutic Surgery, “Laikon” General Hospital of Athens, National and Kapodistrian University of Athens, Athens, Greece

    Ekaterini C. Tampaki & Athanasios Tampakis

  2. Department of Visceral Surgery, Basel University Hospital, Basel, Switzerland

    Athanasios Tampakis

  3. Department of Pharmacology, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias, Goudi, 11527, Athens, Greece

    Constantinos E. Alifieris, Dimitrios Krikelis & Dimitrios T. Trafalis

  4. Department of Medical Oncology, “Henry Dunant” Hospital Center, Athens, Greece

    Constantinos E. Alifieris & Dimitrios T. Trafalis

  5. Department of Surgery, General Hospital of Nea Ionia “Agia Olga-Konstantopouleion”, Athens, Greece

    Constantinos E. Alifieris

  6. Breast Unit, ‘Bioclinic’ General Clinic of Athens, Athens, Greece

    Anastasia Pazaiti

  7. First Department of Surgery, “Laikon” General Hospital of Athens, National and Kapodistrian University of Athens, Athens, Greece

    Michalis Kontos

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  1. Ekaterini C. Tampaki
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Corresponding author

Correspondence to Constantinos E. Alifieris.

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Conflict of interest

Ekaterini C. Tampaki, Athanasios Tampakis, Constantinos E. Alifieris, Dimitrios Krikelis, Anastasia Pazaiti, Michalis Kontos, and Dimitrios T. Trafalis declare that they have no conflicts of interest.

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No funding was received for this work.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in this study.

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Tampaki, E.C., Tampakis, A., Alifieris, C.E. et al. Efficacy and Safety of Neoadjuvant Treatment with Bevacizumab, Liposomal Doxorubicin, Cyclophosphamide and Paclitaxel Combination in Locally/Regionally Advanced, HER2-Negative, Grade III at Premenopausal Status Breast Cancer: A Phase II Study. Clin Drug Investig 38, 639–648 (2018). https://doi.org/10.1007/s40261-018-0655-z

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