Trastuzumab Biosimilar Plus Pertuzumab for HER2-Positive Metastatic Breast Cancer Treated With Chemotherapy

For metastatic breast cancer (mBC) that produces a positive test result for human epidermal growth factor receptor-2 (HER-2), adding dual blockade with trastuzumab and pertuzumab to chemotherapy is recommended as first-line therapy. To determine outcomes of replacing reference trastuzumab with the trastuzumab biosimilar SB3 in this regimen, Danish researchers conducted a retrospective study based on data from the Danish Breast Cancer Group (DBCG) database and found that median progression-free-survival (mPFS) with SB3 was comparable with that for reference trastuzumab (Breast Cancer [Auckl]. 2022;16:1-6. doi:10.1177/11782234221086992).

“Human epidermal growth factor receptor 2 positivity is seen in 15% to 20% of cases of mBC and is associated with an aggressive disease course,” wrote Alan Celik, BSc Med, Danish Breast Cancer Group, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark, and colleagues. “HER2-targeting therapy with trastuzumab and pertuzumab in combination with chemotherapy improves progression-free survival (PFS) and overall survival (OS) in individuals with HER2-positive mBC and is the recommended first-line treatment of patients with HER2-positive mBC.”

In conducting their study, Celik and colleagues extracted data on the primary diagnosis and treatment of all women with HER2-positive mBC who received first-line treatment with SB3 and pertuzumab from September 2018 through February 2020. The study’s dual primary endpoints were overall survival (OS) and PFS.

“SB3, a biosimilar trastuzumab, was approved by the European Medicines Agency (EMA) in 2017 and has since September 2018 replaced trastuzumab for treatment of HER2-positive breast cancer in Denmark due to reimbursement reasons,” Celik and team explained. “SB3 has been compared with trastuzumab in neoadjuvant treatment of early HER2-positive breast cancer, but the effect of SB3 in combination with pertuzumab in a metastatic, real-world setting has not yet been assessed.”

To conduct such an assessment, Celik and colleagues initiated a study that included 117 women who received first-line treatment with SB3 and pertuzumab for HER2-positive mBC; 71 patients, or 61%, had recurrent disease, and 46 patients, or 39%, had de novo mBC. The mean age of the study group patients was 60 years, and the media follow-up was 11.1 months for PFS and 15.4 months for OS.

At 12-month follow-up, OS was 84% (95% confidence interval [CI], 78% to 91%), and the median OS had not yet been reached. Median PFS was 12.7 months (95% CI, 11.1 mo to 16.2 mo). Median time receiving treatment was 8.7 months (95% CI, 7.6 mo to 11.4 mo), and 36 patients were still receiving treatment at the end of the study.

“SB3 as substitute for reference trastuzumab in dual blockade showed comparable mPFS and OS when compared with a similar Danish real-world study with originator trastuzumab,” Celik and colleagues concluded. 

“A population-based observational study from the DBCG published in 2020 examined the efficacy of trastuzumab and pertuzumab in first-line treatment of HER2-positive mBC using real-world data from the DBCG database….The study showed an mPFS of 15.8 months (95% CI, 14.0-19.9) and mOS of 41.8 months (95% CI, 37.7-NE) [in 291 patients]. The mPFS in this study is numerically shorter, but the 95% CIs are overlapping. With an HR of 1.31 (95% CI, 0.98-1.75), we cannot reject that the 2 study cohorts’ PFS are alike.”