In the Phase III HannaH study, the subcutaneous (SC) administration of trastuzumab via a hand-held syringe was shown to be non-inferior to standard intravenous (IV) administration in patients with clinical stage I-III HER2-positive, operable, locally advanced or inflammatory breast cancer, in terms of trough serum concentration and pathological complete response, with a similar safety profile. The purpose of the current study was to assess patient preference for the two administration routes, which has not been assessed previously.
The two-arm crossover study used two telephone interviews (by interviewers who were independent of the study team) to establish patient preference for IV (6mg/kg [8mg/kg loading if de-novo use]) or SC (600mg via single use injection device or hand-held syringe) trastuzumab. Both were administered by healthcare professionals every 21 days for four cycles, with crossover to the alternate for another four cycles. The patient population consisted of 248 women with HER2-positive primary breast cancer with no evidence of residual or recurrent disease following surgery and chemotherapy.
The primary endpoint was the proportion of patients expressing a preference for SC or IV trastuzumab; the assessment of factors affecting preference was exploratory. At the second interview, 216/236 patients (intention-to-treat analysis) preferred SC administration (91.5%; 95% CI 87.2-94.7%; p<0.0001), 16 (6.8%; 3.9-10.8%) preferred IV and four had no preference. The two main reasons people gave for preferring SC were that it either saved time (5 min versus 30-90 min for IV infusion) or resulted in less pain and discomfort.
In their discussion, the authors discuss the advantages of SC administration of trastuzumab, including improved patient convenience, and reduced use of healthcare resources (including the time of healthcare professionals). They say that the results of this study, in combination with those from HannaH, suggest that a fixed dose of 600mg subcutaneous trastuzumab every three weeks is a validated, well tolerated and preferred option of patients for the treatment of HER2-positive breast cancer.
A Comment that accompanied the HannaH study noted the following advantages associated with subcutaneous administration of trastuzumab, whilst acknowledging that these might dissipate when trastuzumab is combined with other IV drugs, especially if trastuzumab biosimilars are available at lower prices.
• Ability to deliver the drug in about 5 minutes without the need to secure IV access makes subcutaneous treatment more convenient.
• Once the drug can be administered at home, patients will be able to continue their lives with less hospital dependence.
• Saving in resources in terms of nurses and cleaning
Trastuzumab for subcutaneous administration (Herceptin SC) has been recommended for approval in the EU for treatment of patients with HER2-positive breast cancer and it is expected to be launched in the UK in 2013 (Quarter 3).