Ontruzant Biosimilar Demonstrates Equivalence to Herceptin in 5-Year Study


The trial included "drifted" (nonstandard) reference product, forcing a stratified analysis to yield relevant data.

Long-term survival findings for the trastuzumab biosimilar Ontruzant (SB3) demonstrated equivalence to the reference product (Herceptin) in a phase 3 study of patients with human epidermal growth factor receptor 2 (HER2)–positive early or locally advanced breast cancer, investigators reported at the 2021 San Antonio Breast Cancer Symposium (SABCS).

Findings were analyzed following a medium of 68 months from patient randomization, constituting the longest monitored data to date for SB3, investigators said.

Previously, at the European Society for Medical Oncology meeting in September 2021, long-term cardiac safety and efficacy results were reported for patients (n = 367) from the same trial. The findings presented at SABCS reflect outcomes for those patients plus an additional 171, as well as stratified, comparative findings for patients exposed to reference drug lots whose quality “drifted,” or was not consistent with the standard, during the trial.

“Patients treated with reference drug ‘drifted’ lots were patients who were exposed to at least 1 vial from reference lots with a downward drift in antibody-dependent cellular cytotoxicity (ADCC) during the neoadjuvant treatment period,” authors of the study wrote.

Patients who were treated with nondrifted lots were those who received reference drug at the standard strength and formulation during the neoadjuvant treatment period.

Investigators said that the 5-year event-free survival (EFS) for patients treated with SB3 vs reference product (drifted or nondrifted) was 79.8% and 75.0%, respectively (HR 0.84; 95% CI, 0.58-1.20; P = .335). Investigators said this still demonstrated equivalence between the biosimilar and the reference product.

The 5-year overall survival (OS) between groups also was comparable: 92.5% for the SB3 group and 85.4% for the reference product group (HR 0.61; 95% CI, 0.36-1.05; P = .073).

“However, there was a meaningful difference within reference product arm depending on the ADCC-drift status,” authors of the study wrote.

In the comparison with nondrifted trastuzumab reference product, the event-free survival for SB3 was 79.8% vs 82.5% for the reference product (HR 1.28; 95% CI, 0.73-2.22; P = .391), and investigators said this demonstrated equivalence.

The OS for patients who received SB3 vs nondrifted reference product was 92.5% vs 91.4% respectively (HR 0.99; 95% CI, 0.42-2.31; P = .975).

They said 5-year EFS for reference drug patients who received drifted vs nondrifted product was 70.3% vs 82.5%, respectively (HR 2.57; 95% CI, 1.28-5.14; P = .008). OS for these 2 groups was 81.3% vs 91.4%, respectively (HR 3.87; 95% CI, 1.37-10.93; P = .011).

“For HER2-positive breast cancer treatment, monitoring long-term outcome is important, and we hope these five-year follow-up study results in a large group of patients provide meaningful value to the oncology society by demonstrating robust comparable long-term safety and efficacy profile of a trastuzumab biosimilar,” said Dong-hoon Shin, vice president and Medical and Lifecycle Safety Team leader for Samsung Bioepis, which developed the biosimilar SB3.

In the phase 3 study, patients were randomly assigned to receive 8 cycles of SB3 or reference drug with concurrent neoadjuvant chemotherapy (4 cycles of docetaxel followed by 4 cycles of 5-fluorouracil/epirubicin/cyclophosphamide).Patients then underwent surgery and went on to receive 10 cycles of SB3 or reference drug based on previous treatment, completing 1 year of treatment.

Following the adjuvant treatment, patients were enrolled in the 5-year follow-up study.


Pivot X, Pegram MD, Cortes J, et al. Final survival analysis of a phase 3 study comparing SB3 (trastuzumab biosimilar) and reference trastuzumab in HER2-positive early or locally advanced breast cancer. Presented at: 2021 San Antonio Breast Cancer Symposium; December 7-10, 2021. Poster P2-13-04.

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