HER2-Positive Breast Cancer Treatment Enters a New Era of Domestic 'Pertruzumab-Trastuzumab' Therapy: Qilu's Dual-Biosimilar Strategy Enhances Treatment Accessibility

Mar 10, 2025 19:10 CST Updated 19:10

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Breast cancer is the malignant tumor with the highest incidence rate among women globally and is also the most common cancer.One of the causes of death^[1] , posing a serious threat to women's health. The breast cancer report published in The Lancet in April 2024 pointed out that 685,000 women still died from this disease in 2020.[2]。Among all breast cancer patients, HER2 (human epidermal growth factor receptor 2) positive breast cancer accounts for 20% to 25% of all breast cancer patients, and it is an aggressive and highly malignant subtype.[3]。

With the acceleration of new drug research and development and faster market entry in China, breast cancer patients have gained access to more diversified clinical options and more accessible treatment choices. On March 8, International Women's Day, the "Exploration and Exchange Conference on the Frontiers of Breast Tumor Diagnosis and Treatment" was held, where the HER2-targeted drug pertuzumab injection (QL1209, Ansaizhu) made its appearance. At the conference, experts and scholars in the field of breast tumors in China gathered to discuss the changes and development trends in breast cancer diagnosis and treatment in the era of precision medicine, as well as the opportunities and challenges in breast tumor treatment.

New Options for Early and Late-Stage HER2-Positive Breast Cancer Patients

The Biosimilar of Pertuzumab is Launched

Under standardized treatment, the 5-year survival rate of breast cancer patients in China has increased to 83.2%, and the 5-year survival rate of early-stage breast cancer patients can reach over 90%.[4]However, the survival of patients with advanced breast cancer remains pessimistic. Data shows that due to the high invasiveness and high malignancy of HER2-positive advanced breast cancer, its 5-year survival rate is 44% lower than that of HER2-negative cases.[5], this particular subgroup always faces more severe challenges in treatment.

In the clinical treatment of HER2-positive breast cancer, pertuzumab is often used in combination with trastuzumab. Trastuzumab[6]and Pertuzumab[7]A monoclonal antibody that precisely targets HER2 inhibits the formation of HER2 dimers by binding to the HER2 protein, blocking the activation of downstream signaling. At the same time, the HER2 epitopes bound by the two are different, and this difference allows the combination of the two to more comprehensively block HER2 signal transduction, thereby significantly enhancing the therapeutic effect.[8]。

In addition, in a phase III clinical trial named CLEOPATRA, 808 patients with HER2-positive advanced MBC were enrolled to compare whether the addition of pertuzumab to trastuzumab combined with chemotherapy could further improve the prognosis of patients with advanced HER2-positive breast cancer.[9]The results showed that the objective response rate was 69.3% in the control group and 80.2% in the pertuzumab group, increasing the response rate by 10.8 percentage points (P=0.001). The combination of the two has thus become the cornerstone of treatment for patients with advanced HER2-positive breast cancer, known in the industry as "Trastuzumab and Pertuzumab dual-targeting."

Against this backdrop, with the expiration of the patent protection period for Pertuzumab and the continuous updating and iteration of biotechnology, Pertuzumab biosimilars targeting specific sites in HER2 and its related signaling pathways have been continuously developed and applied. For instance, at the end of last year, the Pertuzumab biosimilar developed by Qilu Pharmaceutical Co., Ltd. was approved for marketing, providing more diversified options and approaches for the clinical treatment of HER2-positive breast cancer.

It is reported that during the R&D process of QL1209, Qilu Pharmaceutical strictly followed the general principles for the evaluation of biosimilars.[10]In a multicenter, randomized, double-blind, parallel-controlled Phase III clinical trial targeting HER2-positive, ER/PR-negative early or locally advanced breast cancer patients, QL1209 was found to be similar to the original pertuzumab in terms of safety, efficacy, immunogenicity, and pharmacokinetics.

Specifically, the proportion of total pathological complete response (tpCR) assessed by IRC was comparable between the QL1209 group and the reference pertuzumab group (42.75% vs 45.17%), with a relative risk (RR) of 0.95 (90% CI, 0.80-1.11), and the confidence interval (CI) entirely within the predefined equivalence range. In terms of drug safety evaluation, the incidence of treatment-emergent adverse events (TEAEs) was similar between the QL1209 group and the pertuzumab group (95.3% vs 96.1%).[11]

Notably, by the end of June 2024, Qilu Pharmaceutical's Trastuzumab for Injection (brand name: Anqutuo) has officially received marketing approval. Thus, Qilu Pharmaceutical has become the first to achieve the approval of biosimilars for the "Trastuzumab and Pertuzumab dual-target," providing more diversified and accessible treatment options for breast cancer patients, especially those with advanced HER2-positive breast cancer.

"Competition in the Development of 'Quppa Dual-Target' Intensifies"

Helping Patients Access and Afford Medications

In view of the significant clinical efficacy and market potential, the strategic layoutThe number of companies adopting the "dual-target approach of 曲帕" is not small, intensifying market competition.Industry insiders said that the overall pattern of domestically produced "Quppa dual-target" biosimilars in China currently presents a diversified, highly competitive, and rapidly developing situation, which means the market might be entering a stage of fierce "internal competition" or a "red ocean" phase.But correspondingly, with the development and production of more biosimilars, these innovative drugs are establishing new treatment standards for breast cancer patients, providing more options for patient treatment.

Taking the "Qilu Dual-Target" solution of Qilu Pharmaceutical as an example, the attending experts unanimously agreed that the "Qilu Dual-Target" solution is equivalent to the original drug. It is the cornerstone choice for neoadjuvant treatment of HER2-positive early breast cancer and a first-line treatment option for HER2-positive advanced breast cancer, significantly extending the survival of breast cancer patients.

At the same time, based on balancing the safety and efficacy of drugs, the research and application of biosimilars are of great positive significance for alleviating the medication burden of breast cancer patients at the current stage. Therefore, in recent years, the state and relevant regulatory authorities have formulated a series of policies to support the research and application of biosimilars while addressing issues of patient accessibility and affordability.

In 2021, the CDE released the "Technical Guidelines for Biosimilar Similarity Evaluation and Indication Extrapolation"; in 2023, the National Healthcare Security Administration proposed in the "Notice on Key Tasks for Centralized Procurement and Price Management of Pharmaceuticals in 2023" to expand the coverage of centralized procurement, which should include chemical drugs, traditional Chinese medicine, and biologics; in February this year, the Anhui Provincial Healthcare Security Administration officially released the "Key Task List for 2025 of the Anhui Provincial Healthcare Security Administration," clearly stating its leadership in the national biologics alliance procurement.

Notably, although trastuzumab and pertuzumab have been included in the medical insurance catalog, their long-term treatment costs may still impose a certain economic burden on patients' families. With the launch of biosimilars, trastuzumab and pertuzumab have gradually become more affordable, transitioning from once "astronomically priced drugs" to being accessible to the general public. This not only demonstrates the significant advantages of biosimilars in reducing treatment costs and alleviating pressure on medical insurance but also highlights their profound social value in benefiting a wide range of patients and improving drug accessibility.

References

[1]WHO, Global cancer burden growing, amidst mounting need for services, 2024

[2]C.,Coles,H.,Earl,B.,Anderson.et al. The Lancet Breast Cancer Commission. The Lancet(2024). https://doi.org/10.1016/S0140-6736(24)00747-5

[3]HER2-positive breast cancer and tyrosine kinase inhibitors:the time is now[J].NPJ Breast Cancer，2021,7(1):56.

[4]ALLEMANI C, MATSUDA T, DI CARLO V, et al. Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries[J]. Lancet, 2018, 391(10125):1023-1075.

[5]Prognosis of women with metastatic breast cancer by HER2 statusand trastuzumab treatment:aninstitutional-based review.J Clin Oncol.2010 Jan 1;28(1):92-8.

[6]Molina MA, Codony-Servat J, Albanell J, et al. Trastuzumab (herceptin), a humanized anti-Her2 receptor monoclonal antibody, inhibits basal and activated Her2 ectodomain cleavage in breast cancer cells. Cancer Res. 2001 Jun 15;61(12):4744-9.

[7]Franklin MC, Carey KD, Vajdos FF, et al. Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex. Cancer Cell. 2004 Apr;5(4):317-28.

[8]Scheuer W, Friess T, Burtscher H, et al. Strongly enhanced antitumor activity of trastuzumab and pertuzumab combination treatment on HER2-positive human xenograft tumor models. Cancer Res. 2009 Dec 15;69(24):9330-6.

[9]Pertuzumab plus Trastuzumab plus Docetaxel for Metastatic Breast Cancer，N Engl J Med. 2012 Jan 12;366(2):109-19.

[10]Center for Drug Evaluation NMPA. Guiding Principles for Clinical Trials of Biosimilar Pertuzumab Injection.

[The data and opinions in this article are sourced from Qilu Pharmaceutical and do not represent the views of this newspaper.]

Editor: Yu Yuanze

Reviewed by: Ma Fei, Zhang Song

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