While US patients with HER2-positive cancers do not have an available subcutaneous trastuzumab option, Brazil, Canada, and the European Union have an approved product that has been shown in a phase 3 trial to be noninferior to intravenous trastuzumab.
While US patients with HER2-positive cancers do not have an available subcutaneous (SC) trastuzumab option, Brazil, Canada, and the European Union have an approved product that has been shown in a phase 3 trial to be noninferior to intravenous (IV) trastuzumab.
This product has substantial benefits related to patient comfort and provider time, but it also has benefits for trastuzumab’s sponsor, Roche, as there are no approved biosimilars of the SC formulation to compete with this product.
As explained in a paper recently published in Pharmaceutical Medicine, the SC trastuzumab contains the same monoclonal antibody as the intravenous formulation at a dose of 600 mg per 5-mL vial, plus a recombinant human hyaluronidase, to be used every 3 weeks. The hyaluronidase is used to increase the permeability of the extracellular matrix, allowing for administration of higher volumes and enhanced absorption.
The SC formulation had a similar safety profile to the IV formulation in the phase 3 HannaH study, but serious adverse events (AEs) were more common with the SC trastuzumab than the IV product (21.0% vs 12.0%; P value not reported). Antidrug antibodies (ADAs) were reported in 7.1% of patients receiving the IV product and 14.6% of those receiving the SC product, but the elicited ADAs were deemed to have no clinical relevance as they were non-neutralizing and did not impact the pharmacokinetic profile of trastuzumab.
However, one of the main concerns with trastuzumab’s biological activity is its interaction with pertuzumab to treat HER2-positive cancer, and interactions among HER2 receptor, pertuzumab, and trastuzumab—ADA complexes have not yet been fully evaluated. The phase 3 SAPPHIRE study did evaluate the safety, tolerability, and efficacy of IV pertuzumab plus SC trastuzumab and a taxane, but the small population enrolled in the study made it difficult to draw conclusions.
According to the paper’s authors, it also remains unclear whether, in the case of a tumor recurrence, patients who had received the SC product would have more long-lasting memory ADAs, or whether this would impact the safety and efficacy of a subsequent line of treatment using IV trastuzumab and pertuzumab.
Reference
Pimentel FF, Morgan G, Tiezzi DG, de Andrade JM. Development of new formulations of biologics: expectations, immunogenicity, and safety for subcutaneous trastuzumab. Pharmaceut Med. 2018;32(5):319-325. doi: 10.1007/s40290-018-0247-5.
How AI Can Help Address Cost-Related Nonadherence to Biologic, Biosimilar Treatment
March 9th 2025Despite saving billions, biosimilars still account for only a small share of the biologics market—what's standing in the way of broader adoption and how can artificial intelligence (AI) help change that?
Patients With IBD Maintain Therapy 2 Years Post Switching to Infliximab Biosimilar
March 23rd 2025People with inflammatory bowel disease (IBD) who switched to the infliximab biosimilar CT-P13 had higher treatment persistence (84% and 91%) than those new to infliximab (66% and 53%), with no new safety concerns.
Will the FTC Be More PBM-Friendly Under a Second Trump Administration?
February 23rd 2025On this episode of Not So Different, we explore the Federal Trade Commission’s (FTC) second interim report on pharmacy benefit managers (PBMs) with Joe Wisniewski from Turquoise Health, discussing key issues like preferential reimbursement, drug pricing transparency, biosimilars, shifting regulations, and how a second Trump administration could reshape PBM practices.
Biosimilar Approvals Streamlined With Advanced Statistics Amidst Differing Regulatory Requirements
February 25th 2025The FDA and European Medicines Agency (EMA) mandate high similarity between biosimilars and reference products, but their regulatory processes differ, especially with multiple reference products.