Comprehensive Analysis of Comparison of Trastuzumab Reference with Biosimilars in the Treatment of HER2-Positive Breast Cancer: A Review
DOI:
10.29303/jpm.v21i3.11110Published:
2026-05-25Downloads
Abstract
HER2-positive breast cancer is an aggressive subtype of breast cancer characterized by overexpression of the Human Epidermal Growth Factor Receptor-2 (HER2), which is associated with rapid tumor progression, higher metastasis rates, and poor prognosis. Trastuzumab has become one of the main targeted therapies for HER2-positive breast cancer and has significantly improved patient survival outcomes. However, the high cost of reference trastuzumab products such as Herceptin limits patient access, especially in developing countries. Therefore, trastuzumab biosimilars have emerged as more affordable therapeutic alternatives with comparable clinical performance. This review aimed to analyze and compare the efficacy, pharmacokinetic profile, safety, and cost-effectiveness of reference trastuzumab and trastuzumab biosimilars in the treatment of HER2-positive breast cancer. The method used was a systematic literature review of the PubMed and ScienceDirect databases, using keywords related to breast cancer, trastuzumab, and biosimilars. Studies published between 2014 and 2024 were included based on predetermined inclusion and exclusion criteria. The findings demonstrated that several biosimilars, including SB3 (Ontruzant), CT-P6 (Herzuma), PF-05280014 (Trazimera), ABP 980 (Kanjinti), and trastuzumab-dkst (Ogivri), exhibited equivalent efficacy to reference trastuzumab in terms of pathological complete response (pCR), progression-free survival (PFS), overall survival (OS), and disease-free survival (DFS). In addition, biosimilars showed pharmacokinetic, immunogenicity, and cardiac safety profiles comparable to those of the originator product. Biosimilars also provided significant economic advantages by reducing treatment costs and improving patient access to HER2-targeted therapy. In conclusion, trastuzumab biosimilars are effective, safe, and cost-efficient alternatives to reference trastuzumab for HER2-positive breast cancer management and may support more sustainable healthcare systems.
Keywords:
Biosimilars Breast Cancer TrastuzumabReferences
[1] L. O. Iqmy, S. Setiawati, and D. E. Yanti, “Faktor risiko yang berhubungan dengan kanker payudara,” JKM (Jurnal Kebidanan Malahayati), vol. 7, no. 1, pp. 32–36, 2021.
[2] N. Y. RAtnasari and R. R. N. Aysyah, “Efektivitas Penyuluhan Kesehatan Pemeriksaan Payudara Sendiri (SADARI) Terhadap Tingkat Pengetahuan Remaja Putri,” Jurnal Keperawatan GSH, vol. 12, no. 2, pp. 34–39, 2023.
[3] I. Rona and N. Swastika, “Penyuluhan Kesehatan Tentang Periksa Payudara Sendiri (Sadari) Sebagai Upaya Deteksi Dini Kanker Payudara Di MAN 2 Sigli Kabupaten Pidie,” BAKTIMAS: Jurnal Pengabdian pada Masyarakat, vol. 4, no. 3, pp. 156–165, 2022.
[4] WHO, “Breast Cancer,” World Health Organization.
[5] Kemenkes RI, “Kanker Payudara Paling Banyak di Indonesia, Kemenkes Targetkan Pemerataan Layanan Kesehatan,” Redaksi Sehat Negeriku.
[6] A. Rahma and N. B. Khairun, “Peran Human Epidermal Growth Factor Receptor-2 pada Kanker Payudara,” Agromedicine Unila, vol. 5, no. 2, pp. 644–647, 2018.
[7] O. Tredan et al., “Innovative approach for a typology of treatment sequences in early stage HER2 positive breast cancer patients treated with trastuzumab in the French national hospital database,” Cancer Inform., vol. 21, p. 11769351221135134, 2022.
[8] B. Nami, H. Maadi, and Z. Wang, “Mechanisms underlying the action and synergism of trastuzumab and pertuzumab in targeting HER2-positive breast cancer,” Cancers (Basel)., vol. 10, no. 10, p. 342, 2018.
[9] S. M. Swain et al., “Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer,” New England journal of medicine, vol. 372, no. 8, pp. 724–734, 2015.
[10] R. Kongsakon, S. Lochid-Amnuay, N. Kapol, and O. Pattanaprateep, “From research to policy implementation: trastuzumab in early-stage breast cancer treatment in Thailand,” Value Health Reg. Issues, vol. 18, pp. 47–53, 2019.
[11] S. M. Alexeev et al., “Randomized double-blind clinical trial comparing safety and efficacy of the biosimilar BCD-022 with reference trastuzumab,” BMC Cancer, vol. 20, pp. 1–10, 2020.
[12] F. Cardoso et al., “Early breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up,” Annals of oncology, vol. 30, no. 8, pp. 1194–1220, 2019.
[13] Z. Nahleh et al., “Use of biosimilar medications in oncology,” JCO Oncol. Pract., vol. 18, no. 3, pp. 177–186, 2022.
[14] N. Herawati, “Biosimilar: Trend Obat Masa Kini,” Biotrends, vol. 7, no. 1, pp. 14–19, 2016.
[15] U.S. Food and Drug Administration, “Scientific Considerations in Demonstrating Biosimilarity to a Reference Product,” Food and Drug Administration.
[16] H.-C. Kolberg, G. S. Demetriou, and V. Hanes, “Totality of evidence supporting the use of ABP 980, a trastuzumab biosimilar: Practical considerations,” Oncol. Ther., vol. 9, pp. 225–238, 2021.
[17] T. K. Kvien, K. Patel, and V. Strand, “The cost savings of biosimilars can help increase patient access and lift the financial burden of health care systems,” in Seminars in arthritis and rheumatism, Elsevier, 2022, p. 151939.
[18] H. S. Rugo et al., “Final overall survival analysis of the phase 3 HERITAGE study demonstrates equivalence of trastuzumab-dkst to trastuzumab in HER2-positive metastatic breast cancer,” Breast Cancer Res. Treat., vol. 188, no. 2, pp. 369–377, 2021.
[19] S. J. Bae et al., “Real-world clinical outcomes of biosimilar trastuzumab (CT-P6) in HER2-positive early-stage and metastatic breast cancer,” Front. Oncol., vol. 11, p. 689587, 2021.
[20] L. U. Sarder and S. Ahmad, “Emerging role of biosimilars: Focus on trastuzumab and metastatic human epidermal growth factor receptor 2-positive breast cancer,” Results Chem., vol. 6, p. 101055, 2023.
[21] X. Chen, C. Li, R. Ewesuedo, and D. Yin, “Population pharmacokinetics of PF-05280014 (a trastuzumab biosimilar) and reference trastuzumab (Herceptin®) in patients with HER2-positive metastatic breast cancer,” Cancer Chemother. Pharmacol., vol. 84, pp. 83–92, 2019.
[22] S. Matovina et al., “Comparison of Biosimilar Trastuzumab ABP 980 with Reference Trastuzumab in Neoadjuvant Therapy for HER2-positive Breast Cancer–an Analysis of a Large University Breast Cancer Centre,” Geburtshilfe Frauenheilkd., vol. 83, no. 06, pp. 694–701, 2023.
[23] D. Gagliato et al., “Real-World Study of Adjuvant Biosimilar Trastuzumab-dkst for HER2-Positive Breast Cancer Treatment in a Brazilian Population,” Oncol. Ther., pp. 1–13, 2024.
[24] J. Stebbing et al., “Six-year survival outcomes for patients with HER2-positive early breast cancer treated with CT-P6 or reference trastuzumab: observational follow-up study of a phase 3 randomised controlled trial,” BioDrugs, vol. 37, no. 3, pp. 433–440, 2023.
[25] X. Pivot et al., “A phase III study comparing SB3 (a proposed trastuzumab biosimilar) and trastuzumab reference product in HER2-positive early breast cancer treated with neoadjuvant-adjuvant treatment: final safety, immunogenicity and survival results,” Eur. J. Cancer, vol. 93, pp. 19–27, 2018.
[26] R. K. Li et al., “Long-term safety and effectiveness of PF-05280014 (a trastuzumab biosimilar) treatment in patients with HER2-positive metastatic breast cancer: updated results of a randomized, double-blind study,” BioDrugs, vol. 36, no. 1, pp. 55–69, 2022.
[27] Y. Huang et al., “Longitudinal MRI-based fusion novel model predicts pathological complete response in breast cancer treated with neoadjuvant chemotherapy: a multicenter, retrospective study,” EClinicalMedicine, vol. 58, 2023.
[28] C. Muñoz et al., “Comparative Effectiveness and Safety of Trastuzumab Biosimilars to Herceptin for Adjuvant Treatment of HER2+ Breast Cancer,” Current Oncology, vol. 31, no. 3, pp. 1633–1644, Mar. 2024, doi: 10.3390/curroncol31030124.
[29] X. Ye et al., “Efficacy and safety of biosimilar trastuzumab (HLX02) in patients with HER2-positive advanced breast cancer: a retrospective real-world analysis,” Front. Oncol., vol. 15, 2025, doi: 10.3389/fonc.2025.1622854.
[30] M. Masse, “382P FES PET/CT predictive value of late hormone therapy rechallenge efficacy in metastatic breast cancer,” ESMO Open, vol. 10, p. 104953, May 2025, doi: 10.1016/j.esmoop.2025.104953.
[31] K. Kaushal, V. Thummar, and P. Mehta, “Real-World Evaluation of Trastuzumab Emtansine Biosimilar in Early-Stage HER2-Positive Breast Cancer: Results from a Single-Center Retrospective Study in India,” Archives of Breast Cancer, vol. 13, no. 2, pp. 182–189, Apr. 2026, doi: 10.32768/abc.2906718345-529.
[32] E. Triantafyllidi and J. K. Triantafillidis, “Systematic Review on the Use of Biosimilars of Trastuzumab in HER2+ Breast Cancer,” Aug. 01, 2022, MDPI. doi: 10.3390/biomedicines10082045.
[33] X. Pivot et al., “Cardiac Safety and Efficacy of SB3 Trastuzumab Biosimilar for ERBB2-Positive Early Breast Cancer: Secondary Analysis of a Randomized Clinical Trial,” JAMA Netw. Open, vol. 6, no. 4, p. E235822, Apr. 2023, doi: 10.1001/jamanetworkopen.2023.5822.
[34] A. Bernat-Peguera et al., “Efficacy of CT-P6 (trastuzumab biosimilar) versus reference trastuzumab in combination with pertuzumab in HER2-positive early-stage breast cancer: Preclinical and real-life clinical data,” Breast, vol. 62, pp. 1–9, Apr. 2022, doi: 10.1016/j.breast.2022.01.007.
[35] R. Zhang, X. Liu, G. Song, Y. Zhang, and H. Li, “Trastuzumab Biosimilar (HLX02), Pertuzumab Plus Chemotherapy in Patients with HER2-Positive Metastatic Breast Cancer after Progression of Trastuzumab: A Prospective, Phase II Study,” Cancer Res. Treat., vol. 56, no. 3, pp. 795–801, Jul. 2024, doi: 10.4143/crt.2023.1151.
[36] C. Schwabe, C. Wynne, D. R. Dyapa, A. Prajapati, and D. Dadke, “Pharmacokinetics, Safety, Tolerability, and Immunogenicity of BP02 (Trastuzumab Biosimilar) Compared to EU- and US-Approved Trastuzumab in Healthy Adult Male Volunteers: A Phase 1, Randomized, Double-Blind Study,” Oncol. Ther., vol. 12, no. 3, pp. 477–490, Sep. 2024, doi: 10.1007/s40487-024-00289-0.
[37] C. F. Waller et al., “A pharmacokinetics phase 1 bioequivalence study of the trastuzumab biosimilar MYL-1401O vs. EU-trastuzumab and US-trastuzumab,” Br. J. Clin. Pharmacol., vol. 84, no. 10, pp. 2336–2343, Oct. 2018, doi: 10.1111/bcp.13689.
[38] F. J. Esteva, J. Stebbing, R. N. Wood-Horrall, P. J. Winkle, S. Y. Lee, and S. J. Lee, “A randomised trial comparing the pharmacokinetics and safety of the biosimilar CT-P6 with reference trastuzumab,” Cancer Chemother. Pharmacol., vol. 81, no. 3, pp. 505–514, Mar. 2018, doi: 10.1007/s00280-017-3510-7.
[39] H. Zhou et al., “A randomized Phase I pharmacokinetic trial comparing the potential biosimilar trastuzumab (SIBP-01) with the reference product (Herceptin®) in healthy Chinese male volunteers,” Expert Opin. Drug Metab. Toxicol., vol. 16, no. 10, pp. 997–1003, Oct. 2020, doi: 10.1080/17425255.2020.1807935.
[40] J. H. Park et al., “Efficacy and Safety of Trastuzumab Biosimilar (CT-P6) Compared With Reference Trastuzumab in Patients With HER2-positive Advanced Gastric Cancer A Retrospective Analysis,” American Journal of Clinical Oncology: Cancer Clinical Trials, vol. 45, no. 2, Feb. 2022, doi: 10.1097/COC.0000000000000887.
[41] X. Chen, C. Li, R. Ewesuedo, and D. Yin, “Population pharmacokinetics of PF-05280014 (a trastuzumab biosimilar) and reference trastuzumab (Herceptin®) in patients with HER2-positive metastatic breast cancer,” Cancer Chemother. Pharmacol., vol. 84, no. 1, pp. 83–92, Jul. 2019, doi: 10.1007/s00280-019-03850-1.
[42] S. M. Alexeev et al., “Randomized double-blind clinical trial comparing safety and efficacy of the biosimilar BCD-022 with reference trastuzumab,” BMC Cancer, vol. 20, no. 1, Aug. 2020, doi: 10.1186/s12885-020-07247-9.
[43] C. A. Ferrara and P. L. Ferrara, “Cost-effectiveness and efficacy analysis of biosimilar drugs for lung diseases: a systematic review,” Dec. 15, 2025, Emerald Publishing. doi: 10.1108/JES-01-2025-0059.
[44] X. Luo et al., “Clinical Benefit, Price, and Uptake for Cancer Biosimilars vs Reference Drugs in China: A Systematic Review and Meta-Analysis,” JAMA Netw. Open, vol. 6, no. 10, p. E2337348, Oct. 2023, doi: 10.1001/jamanetworkopen.2023.37348.
[45] H. U. Kim et al., “The Future of Biosimilars: Maximizing Benefits Across Immune-Mediated Inflammatory Diseases,” Drugs, vol. 80, no. 2, pp. 99–113, Feb. 2020, doi: 10.1007/s40265-020-01256-5.
[46] T. K. Kvien et al., “Beyond Cost: Observations on Clinical and Patient Benefits of Biosimilars in Real-World Settings,” Jul. 01, 2025, Adis. doi: 10.1007/s40259-025-00727-z.
[47] X. Du et al., “Assessment of clinical benefit, cost and uptake of biosimilars versus reference biologics in immune-mediated inflammatory diseases in China,” Front. Public Health, vol. 12, 2024, doi: 10.3389/fpubh.2024.1476213.
[48] J. Al-Saleh, A. A. Negm, A. Almarzooqi, N. E. E. Elsidig, and N. Zamani, “Analysis of Cost-Effectiveness of Biologic Therapies in Axial Spondyloarthritis Based on Real-World Data,” ClinicoEconomics and Outcomes Research , vol. 17, pp. 915–930, 2025, doi: 10.2147/CEOR.S556012.
[49] S. Lochid-Amnuay and R. Kongsakon, “Economic Evaluation and Budget Impact of Biosimilar Trastuzumab for HER2-Positive Metastatic Breast Cancer in Thailand: Policy Implications for Access and Affordability.” [Online]. Available: www.elsevier.com/locate/vhri
[50] K. Peng et al., “Cost-Effectiveness of Biosimilars vs Leflunomide in Patients with Rheumatoid Arthritis,” JAMA Netw. Open, vol. 7, no. 6, p. e2418800, Jun. 2024, doi: 10.1001/jamanetworkopen.2024.18800.
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