Page 119 - EJMO-9-3

Eurasian Journal of
Medicine and Oncology Zercepac + pyrotinib versus pertuzumab in HER2+ BC
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1. Introduction by the National Medical Products Administration in 2020.
In a global phase III clinical study, patients with HER2-
Breast cancer is the most common malignancy among positive advanced (recurrent or metastatic) breast cancer
women and ranks first in the incidence rate of female treated with Zercepac in combination with docetaxel had
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malignant tumors. The incidence and mortality rates of an objective response rate (ORR) at week 24 similar to that
breast cancer have been increasing year by year, posing
a serious threat to women’s physical and mental health. of the control group receiving trastuzumab plus docetaxel,
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indicating comparable efficacy. In addition, the safety study
Human epidermal growth factor receptor 2 (HER2)- results showed no statistically significant difference in the
positive breast cancer accounts for approximately 20 5
– 30% of all breast cancer cases. HER2-positive breast incidence of adverse events between the two drugs. An
cancer is characterized by strong invasiveness and poor American expert panel stated that biosimilars and reference
prognosis. Over two decades ago, HER2-positive breast products could be considered equally efficacious for the
cancer had the highest recurrence rate and the worst purpose of inclusion in the American Society of Clinical
prognosis among all subtypes. However, the advent of Oncology clinical practice guidelines, recommending that
trastuzumab – a humanized monoclonal antibody and individual institutions review approved biosimilars with
the first anti-HER2 targeted drug – in 1998 significantly their appropriate drug committees before implementation
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improved outcomes for patients with this disease. In recent on their formularies. Zercepac has also been approved
years, an increasing number of new targeted therapies by the China Food and Drug Administration for the
have been approved, further enhancing the survival and neoadjuvant treatment of breast cancer.
prognosis of HER2-positive patients. Present data indicate Trastuzumab, a HER2-targeted monoclonal
that the survival rate of patients with early-stage HER2- antibody, has been proven to significantly improve
positive breast cancer receiving chemotherapy and dual the survival outcomes of patients with HER2-
antibody therapy exceeds 90%. Neoadjuvant therapy, an positive breast cancer when used in combination
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important treatment modality for HER2-positive breast with other chemotherapy drugs. However, after more
cancer, not only facilitates tumor shrinkage, downstaging, than 20 years of use, many patients have developed
and increased rates of breast-conserving surgery, but resistance, leading to recurrence and metastasis. To
also provides pivotal evidence for optimizing subsequent address these clinical challenges and improve the
adjuvant treatment strategies. prognosis of patients with HER2-positive breast
Trastuzumab is the first-line treatment for HER2- cancer, new HER2-targeted drugs, specifically small
positive breast cancer, but it is relatively expensive, making molecule tyrosine kinase inhibitors (TKIs), have
it difficult for some patients to afford. With the expiration emerged. Pyrotinib (Py) is an irreversible pan-HER
of the Herceptin patent, attention has shifted toward the small molecule TKI that acts simultaneously on HER1,
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development of more affordable biosimilars. The European HER2, and HER4. Results from the phase III PHEDRA
Medicines Agency defines a biosimilar as a biological study confirmed that the Py + trastuzumab + docetaxel
product that is highly similar to an existing reference regimen significantly increased the pathological
product, with no clinically meaningful differences in terms complete response (pCR) rate in patients with HER2-
of efficacy and safety. Safety mainly refers to the clinical positive breast cancer during neoadjuvant treatment.
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safety of subjects or patients. Therefore, in addition to Based on this study, Py was approved in 2022 for the
demonstrating similarity in structure, purity, and biological neoadjuvant treatment of HER2-positive breast cancer.
activity, biosimilars must undergo clinical trials to confirm However, there are few reports on the efficacy and
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their efficacy and safety. Biosimilars also occupy a place in adverse events of Zercepac in combination with Py
clinical applications due to their unique cost advantage. or pertuzumab and chemotherapy in neoadjuvant
In 2020, the “Expert Consensus on Biosimilars” issued chemotherapy (NAT) for HER2-positive breast cancer.
in China pointed out that biosimilars are not the same This study retrospectively analyzed the clinical and
as generic drugs. The main clinical data requirements for pathological data of 62 patients with HER2-positive
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generic drugs are pharmacokinetics and bioequivalence, breast cancer who received Zercepac in combination
while biosimilars must also conduct safety and efficacy with Py or Zercepac in combination with pertuzumab
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studies on this basis and support the equivalence of and chemotherapy as a NAT regimen, and who
efficacy and safety between biosimilars and reference subsequently underwent surgery. The efficacy and
drugs, allowing them to be used clinically as substitutes adverse reactions were observed and recorded, and the
for reference drugs. Zercepac (HLX02) is a domestically factors affecting the pCR rate were analyzed, with the
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developed trastuzumab biosimilar approved for clinical use aim of providing references for clinical treatment.
Volume 9 Issue 3 (2025) 111 doi: 10.36922/EJMO025100044