For patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC), FDA approval of trastuzumab in 1998 was a game changer. Between 1998 and 2019, the only formulation of trastuzumab that was available in the United States was the IV form of the biological agent.  The release of a SC formulation as well as that of several biosimilars followed the expiration of trastuzumab’s patent in 2019.

A recent review compared the pharmacokinetics (PK), efficacy, and safety of IV and SC trastuzumab. It also explored additional therapeutic considerations such as route of administration, patient preference, cost associated with the SC and IV trastuzumab formulations, and costs associated with trastuzumab biosimilars.

The PK of SC trastuzumab was compared with that of IV trastuzumab in two open-labeled studies involving healthy volunteers and women with early HER2-BC. In one study, 8 mg/kg SC trastuzumab produced similar PK values to 6 mg/kg IV trastuzumab, with both yielding a half-life of about 10 days. Similar trough levels were found during predose cycle 9 measurements, which were taken prior to surgery, as well as in pathological complete response (pCR). However, there is concern that in obese patients (i.e., >80 kg), a fixed-dose SC regimen of 600 mg trastuzumab may not be as effective as the IV dose of 6 mg/kg due to weight-related PK differences. Further research is needed in this area.

Overall, comparable efficacy was observed between the IV and SC formulations of trastuzumab. Differences in pCR, overall response (i.e., clinical complete response or partial tumor response), median time to response, and 6-year event-free survival were not statistically significant between the two agents.

The most common adverse events with IV trastuzumab were infections, headache, nausea, fever, and chills, whereas for the SC formulation they included diarrhea, fatigue, and arthralgia. One study showed that while the rates of adverse events between IV and SC trastuzumab were similar, there were more serious adverse events (e.g., febrile neutropenia) in the latter group (20.9% vs. 12.4%, respectively). The SC formulation was associated with more immunogenicity, with twice as many patients in this group developing postbaseline antidrug antibodies to trastuzumab compared with the IV group (6.8% vs. 3.4%, respectively).

The SC formulation was associated with antirecombinant human hyaluronidase PH-20 antibodies. This occurred because of the addition of recombinant human hyaluronidase to the SC formulation, which is used to degrade hyaluronidase, thereby disrupting the barrier between cells under the skin and allowing for more rapid dispersion and absorption of the biologic. Crossover studies between the IV and SC formulations revealed higher rates of adverse events for the latter preparation, but rates of discontinuation and cardiac adverse events were similar between the groups and no new safety signals were observed.

Other factors to take into consideration when choosing between the IV and SC formulation include route of administration and whether a patient already has a port in place; time for drug administration, which is 90 minutes for the IV infusion versus 2 to 5 minutes for the SC injection; time on the healthcare unit, which may be an important factor during the COVID-19 pandemic; greater flexibility in scheduling with the SC formulation; patient preferences, which tend to favor SC administration; and cost. Cost should consider not only the acquisition price of trastuzumab formulation but also healthcare provider time.

Shorter administration time with the SC form may be more cost-effective, but the patient-observation period following administration of the biologics is similar. The price of reference IV trastuzumab and SC trastuzumab should also be weighed against the price of trastuzumab biosimilars, which can offer a cost saving of about 30% (to up to 69%) compared with the reference product as well as to the SC fixed-dose combination of pertuzumab and trastuzumab.

This review assists the pharmacist in making formulary decisions by weighing the advantages and disadvantages of various commercially available trastuzumab formulations.

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.

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