Subcutaneous herceptin therapy

Abstract

In a recent issue of the Journal of Clinical Pharmacology, we noted with interest the paper by Wynne et al1 which compared subcutaneous and intravenous administration of trastuzumab in a Phase l/lb trial in healthy male volunteers and patients with HER-2 positive breast cancer. As discussed in the paper, the potential benefits of such a formulation of traztuzumab include significantly reduced administration time, reducing time commitments for patients and health care workers and improved convenience. It may also be associated with improved compliance and a reduction in the frequency and/or intensity of infusion-related reactions.2 While the use of a novel formulation of traztuzumab is certainly welcome, we are concerned about potential under dosing and as such under treating of overweight and obese patients with this formulation which uses standard dose for all patients in contrast to mg/kg individualised intravenous dosing used heretofore. Obesity is an established risk factor for the development of breast cancer3 and is also independently associated with poorer breast cancer outcomes overall in both pre- and post-menopausal women.4 Ogden et al5 in the National Health and Nutrition Examination Survey assessed the prevalence of obesity in the US and reported that more than one-third of adults were obese in 2009–2010. Similar figures exist in Ireland, with at least a third of Irish adults being overweight and a quarter obese.6 Mean body mass index (BMI) for patients included in the Wynne et al study was 17.3–48.3 kg/m2, with the majority falling into the normal weight (18.5–24.9 kg/m2) and overweight (25–29.9 kg/m2) categories. Analysis of all patients (n = 1,041) receiving adjuvant breast cancer chemotherapy at one of our centers from 2001 to 2010 showed the overweight and obese (BMI > 30) categories to be representative of more than 60% of the total; more than 20% of patients weighed more than 80 kg (Figure 1). Cancer-specific outcomes tend to be worse in obese patient groups. The American Society of Clinical Oncology believe that less than full weight-based dosing and unnecessary dose reductions may explain, to some extent, the significantly higher cancer mortality rates seen in the overweight and obese patient groups.7 This would be of particular concern in patients with chemoresponsive and potentially curable disease. Such observations highlight the need for additional evaluations for dosing of subcutaneous herceptin in obese and overweight patients.