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.
Reference
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.
Challenges and Guidance in Biosimilar Assessment: An ISPOR Report on HTA Agency Approaches
May 14th 2024The ISPOR report highlights the urgent need for clear guidance on when and how to conduct health technology assessments (HTAs) for biosimilars, emphasizing the challenges faced by HTA agencies and the evolving role of HTAs in evaluating biosimilar value.
Biosimilars Policy Roundup for April 2024—Podcast Edition
May 5th 2024On this episode of Not So Different, The Center for Biosimilars® glances back at all the major biosimilar policy updates from April, including 2 FDA approvals, 1 European approval, and several insights into possible policy changes from the Festival of Biologics USA conference.
A New Chapter: How 2023 Will Shape the US Biosimilar Space for 2024 and Beyond
December 31st 2023On this episode of Not So Different, Cencora's Brian Biehn and Corey Ford take a look back at major policy and regulatory advancements in 2023 and how these changes will alter the space going forward.
Dr Sophia Humphreys Provides Calls to Action to Ensure Biosimilar Market Sustainability
April 30th 2024During her presentation during Festival of Biologics USA, Sophia Humphreys, PharmD, director of formulary management at Sutter Health, gave an overview of current challenges and opportunities for the biosimilar market and offered calls to action for multiple stakeholders.