Trastuzumab Biosimilar and Pertuzumab Effective, Safe in Neoadjuvant Breast Cancer Therapy

The combination of trastuzumab biosimilar and pertuzumab with chemotherapy was effective in treating HER2-positive breast cancer, offering high safety and affordability.

Trastuzumab biosimilar (Zercepac) and pertuzumab (Perjeta) combined with chemotherapy regimens showed efficacy among patients with HER2-positive breast cancer, according to a study published in the Asian Journal of Surgery.¹

HER2-positive breast cancer accounts for about 15% to 25% of all molecular subtypes. Common forms of neoadjuvant therapy for this cancer include targeted medications combined with chemotherapy, whereas adjuvant therapies are often forms of surgery.² The European Medicines Agency (EMA) approved the trastuzumab biosimilar in 2020 after a series of comparative quality, preclinical, and clinical studies confirmed its similar efficacy and safety to the reference product.³

The trastuzumab biosimilar is administered through an intravenous drip into a vein for over 90 minutes either once a week or once every 3 weeks for patients with breast cancer.⁴ Typically, patients endure treatment for a year or until the disease returns. However, treatment for metastatic breast cancer continues for as long as necessary.

The EMA approved pertuzumab for combination use with trastuzumab and docetaxel for adult patients with HER2-positive metastatic or locally recurrent unresectable breast cancer in 2013.⁵ Pertuzumab is infused into the vein at a recommended first dose of 840 mg over 60 minutes, followed by a 420 mg dose every 3 weeks, with each dose administered over half an hour to 1 hour.⁶

Researchers aimed to conduct a single-arm real-world study to evaluate the efficacy and safety of trastuzumab biosimilar and pertuzumab combined with other chemotherapy regimens for patients with HER2-positive early or locally advanced breast cancer.¹ The primary endpoint was the total pathological complete response (CR), and secondary endpoints were breast pathological CR, objective response rate (ORR), and disease control rate (DCR).

Participants included 22 female patients with HER2-positive breast cancer who received neoadjuvant therapy with a trastuzumab biosimilar and pertuzumab combined with chemotherapy, followed by surgery after 4 to 8 cycles of treatment. Breast cancer was in the left breast of 14 patients and right breast of 8 patients.

Variations of surgery included modified radical surgery (n = 7), mastectomy with sentinel lymph node biopsy (n = 6), and breast-conserving surgery (n = 9). Pathological evaluations found 15 patients achieved CR while 7 patients reached PR; 3 patients displayed CR in the primary breast lesion but had residual tumor cells in lymph nodes.

The study cohort had a breast pathological CR of 81.8%, a total pathological CR of 68.2%, and a breast retention rate of 40.9%. The combination of trastuzumab biosimilar and pertuzumab was comparable to the originator trastuzumab drug (Herceptin) at a 440 mg dose.

The study had a 100% ORR and DCR, meaning all patients achieved these efficacy end points.Most patients received the TCbHP regimen, a combination of 75 mg/m2 docetaxel and 6 mg/mL/min of carboplatin.⁷ The other patients received the THP regimen (docetaxel, trastuzumab, and pertuzumab) or EC sequential THP (epirubicin and cyclophosphamide combined with THP).⁸

The study was limited due to the small sample size. However, its findings indicate that trastuzumab biosimilar and pertuzumab targeted treatment is effective among patients with HER2-positive breast cancer and offers high safety at low costs. Further research is required to support these findings, which could support the utilization of trastuzumab biosimilar in clinical practice.

References

1. Bao YF, Yang JZ, Li XF, Zhu JJ. Real-world clinical study of trastuzumab biosimilar (Zercepac) and pertuzumab (Perjeta) in combination with chemotherapy for neoadjuvant treatment of HER-2-positive breast cancer. Asian J Surg. 2024;47(7):3225-3228. doi:10.1016/j.asjsur.2024.03.063
2. Burstein HJ, Hayes DF, Vora SR. Patient education: treatment of early HER2-positive breast cancer (beyond the basics). UpToDate. October 12, 2022. Accessed September 16, 2024. https://www.uptodate.com/contents/treatment-of-early-her2-positive-breast-cancer-beyond-the-basics/print
3. Henlius and Accord Healthcare receive EMA approval for Zercepac, trastuzumab biosimilar. News release. Henlius. July 29, 2020. Accessed September 16, 2024. https://www.henlius.com/en/NewsDetails-2670-26.html#:~:text=The%20approval%20was%20based%20on
4. ‌Zercepac. European Medicines Agency (EMA). July 28, 2020. Accessed September 16, 2024. https://www.ema.europa.eu/en/medicines/human/EPAR/zercepac#:~:text=It%20is%20given%20by%20infusion
5. Boix-Perales H, Borregaard J, Jensen KB, et al. The European Medicines Agency Review of Pertuzumab for the treatment of adult patients with HER2-positive metastatic or locally recurrent unresectable breast cancer: summary of the scientific assessment of the committee for medicinal products for human use. Oncologist. 2014;19(7):766-773. doi:10.1634/theoncologist.2013-0348
6. ‌Perjeta. European Medicines Agency. September 17, 2018. Accessed September 16, 2024. https://www.ema.europa.eu/en/medicines/human/EPAR/perjeta
7. Lv M, Guo H, Wang C, et al. Neoadjuvant docetaxel with or without carboplatin plus dual HER2 blockade for HER2-positive breast cancer: a retrospective multi-center Chinese study. Gland Surg. 2020;9(6):2079-2090. doi:10.21037/gs-20-791
8. ‌EC chemotherapy. Breast Cancer Now. Accessed September 16, 2024. https://breastcancernow.org/about-breast-cancer/treatment/chemotherapy/chemotherapy-drugs/ec-chemotherapy/