Study: Trastuzumab Biosimilar IV Offers Better Value Than Reference SC

Trastuzumab biosimilars are available in intravenous (IV) but not subcutaneous (SC) form, and although the SC form of originator trastuzumab is often preferred, IV biosimilars may offer the better deal from the standpoints of cost and convenience, investigators concluded in a recent review of trastuzumab options.

“It is therefore important for health care providers to consider the potential benefits of IV trastuzumab biosimilars (eg, lack of need for additional injections) and whether they outweigh the benefits associated with SC administration, as well as to consider patient preferences,” the authors wrote. The review outlined the current options available for trastuzumab therapy to aid decision-making by health care providers.

Trastuzumab, a monoclonal antibody to human epidermal growth factor receptor 2 (HER2), is used to treat HER2-positive breast cancer and metastatic gastric cancer. According to the authors, combined with chemotherapy, biologics including trastuzumab “have emerged as paradigm-shifting treatments for patients with HER2-positive breast cancer, significantly improving patient outcomes and survival rates.”

The IV formulation of trastuzumab was approved by the FDA in 1998. An SC formulation was approved (for HER2-positive breast cancer only) by the European Medicines Agency in 2013 and FDA in 2019.

The reviewers noted a drawback of trastuzumab, as with other biologics, is its high cost. Since patent expirations in the European Union and United States, multiple trastuzumab biosimilars have been approved in these 2 regions, all formulated for IV use only. The patent on the SC formulation is set to expire in 2030 in the United States, precluding the availability of biosimilars using the SC route of administration for almost a decade.

Comparable pharmacological and clinical parameters

The authors noted that several studies have investigated the dose of SC trastuzumab required to produce similar pharmacokinetic parameters and serum trough concentrations to the IV formulation and that several studies have compared the efficacy and safety of IV vs SC trastuzumab. Collectively, according to the authors, these studies demonstrate that the IV and SC formulations have “generally comparable pharmacological and clinical profiles” in patients with HER2-positive breast cancer.

However, they acknowledged some questions do remain. The authors said the effect of body weight on the efficacy of each of the 2 formulations might “require additional evaluation.” Additionally, they noted that one study found twice as many patients taking the SC formulation compared with the IV form (6.8% vs 3.4%) developed antidrug antibodies. They also cited 2 trials that evaluated switching between the formulations. In one trial, adverse events (AEs) were similar in patients switched from SC to IV or IV to SC adjuvant therapy for HER2-positive early breast cancer. In a similar study of patients with metastatic breast cancer, there were more AEs in patients during the SC treatment compared with the IV treatment (67.6% vs 44.1%).

Patient preference

Each formulation may offer “unique advantages to patients depending on their individual needs,” the reviewers wrote. They noted the potential for pain at the injection site associated with the SC formulation, due to the large (5 mL) injection volume, and recommended health care providers discuss this with their patients.

The authors suggested that for patients receiving trastuzumab as monotherapy, SC administration could be a time-saving option in that it requires only 2 to 5 minutes vs 30 to 90 minutes for IV administration.

They concluded that as an adjuvant therapy, the SC formulation probably does not present an advantage in time or convenience to the patient, because trastuzumab would likely be combined with another IV therapy, and in many cases, the patient would have a central venous port in place. Therefore, IV administration could be more convenient for these patients, avoiding an additional injection. Contrary to this practicality, the patients in the 2 formulation-switching studies the authors cited overwhelmingly preferred SC administration (88.9% and 85.9%) over IV administration.

Cost of IV vs SC treatment

The authors cited 2 time-and-motion studies, 1 in the United Kingdom and 1 in Belgium. Both found higher costs associated with IV treatment compared with SC treatment. Based on the United Kingdom study, the authors estimated that over a full treatment course (18 cycles), SC trastuzumab would cost approximately $2826 less per patient. The authors noted limitations in both studies; in particular, they did not consider the cost of insertion, maintenance, and potential complications associated with IV catheters.

Cost of reference product vs biosimilars

The authors argued that the discussion of cost savings associated with the SC administration route compared with the IV route “have predominantly overlooked the possible cost benefits of IV trastuzumab biosimilars.” However, patent expirations for the trastuzumab reference product were recent (European Union, 2014; United States, 2019), and therefore, they wrote, this limits “a comprehensive assessment of economic benefits.”

A budget impact analysis the authors cited estimated potential cost savings associated with trastuzumab biosimilars in 28 European countries, estimating cost savings between $1.1 billion and $2.74 billion during the first 5 years, and an additional 55,000 to 116,000 patients able to access trastuzumab therapy.

Trastuzumab biosimilars could improve access by giving physicians a lower-cost option to prescribe. According to the authors’ review of the literature, health care providers may be hesitant to prescribe biologics, despite their efficacy, because of their high cost. They cited a 2014 survey that found “nearly half of oncologists would increase the prescription of anti-HER2 biologics across multiple settings if a lower-cost biosimilar was available.”

The reviewers viewed IV trastuzumab biosimilars as having more potential for cost savings compared with the SC formulation of the reference product. “Given the general reduction in cost associated with the introduction of a biosimilar to the market, it is unlikely that the reduced administration costs associated with the SC formulation of trastuzumab will outweigh the lower cost of IV biosimilars,” they wrote.

Reference

Waller CF, Möbius J, Fuentes-Alburo A. Intravenous and subcutaneous formulations of trastuzumab, and trastuzumab biosimilars: implications for clinical practice. Br J Cancer. Published online February 16, 2021. doi:10.1038/s41416-020-01255-z