ArticlesPreference for subcutaneous or intravenous administration of trastuzumab in patients with HER2-positive early breast cancer (PrefHer): an open-label randomised study
Introduction
Treatment regimens containing trastuzumab administered intravenously are the standard of care for patients with HER2-positive breast cancer. Trastuzumab provides a significant survival benefit in early-stage disease when given as adjuvant therapy for 12 months,1, 2, 3, 4, 5, 6, 7, 8 and in first-line treatment of metastatic disease.9, 10
Intravenous trastuzumab is administered according to bodyweight over 30–90 min in once-weekly or 3-weekly cycles. A subcutaneous formulation, containing a fixed dose of 600 mg trastuzumab and 10 000 U recombinant human hyaluronidase (rHuPH20, Halozyme Therapeutics, San Diego, CA, USA) as an excipient, has been developed for 3-weekly use as an alternative to the intravenous formulation. A single-use injection device provides an alternative to subcutaneous injection via hand-held syringe, and can enable self-administration.11 Pharmacokinetic bioequivalence between the two methods of subcutaneous administration was shown in the CP3 study (NCT01344863).11 Subcutaneous trastuzumab was well tolerated using both methods, with no grade 4 or 5, cardiac, or serious adverse events reported.11
The phase 3 HannaH study12 met its coprimary endpoints of non-inferior serum trough concentration and pathological complete response with neoadjuvant or adjuvant subcutaneous trastuzumab via hand-held syringe versus intravenous trastuzumab in 596 patients. The overall safety profile of subcutaneous trastuzumab was consistent with the known safety profile of intravenous treatment in early breast cancer.12 However, patient preference for route of administration has not been assessed to date.
The Preference for Herceptin SC or IV Administration (PrefHer) study was designed to assess patient preference for trastuzumab administered either subcutaneously or intravenously in the adjuvant breast cancer setting.
Section snippets
Study design and patients
PrefHer was an international, multicentre, open-label, randomised, two-cohort, two-arm, crossover study which used comprehensive telephone interviews to determine patient preference for route of administration of trastuzumab. The study design is shown in figure 1. Eligible patients were women aged 18 years or older with HER2-positive (immunohistochemistry 3+ or positive by in-situ hybridisation), histologically confirmed primary invasive breast adenocarcinoma, no evidence of residual, locally
Results
From Oct 27, 2011, to March 29, 2012, 265 patients completed the first interview, and 248 patients were randomised (figure 2) at 56 centres in Europe and Canada. Four randomised patients did not receive study treatment, so the safety population consisted of 244 patients: 122 per study group. Ten patients who were treated did not complete all eight cycles of trastuzumab, owing to disease recurrence (four), adverse events (three), withdrawal of consent (one), loss to follow-up (one), and refusal
Discussion
PrefHer showed that patients preferred fixed-dose subcutaneous delivery of trastuzumab via a single-use injection device over standard intravenous administration for the treatment of HER2-positive early breast cancer (panel).
Confirmed advantages of subcutaneous trastuzumab administration include improved patient convenience (injection time less than 5 min vs 30–90 min for intravenous administration,13 which is important in long-term or single-agent trastuzumab therapy) and reduced use of
References (25)
- et al.
2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial
Lancet
(2007) - et al.
Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2-positive early breast cancer: a 4-year follow-up of a randomised controlled trial
Lancet Oncol
(2011) - et al.
Subcutaneous versus intravenous administration of (neo)adjuvant trastuzumab in patients with HER2-positive, clinical stage I–III breast cancer (HannaH study): a phase 3, open-label, multicentre, randomised trial
Lancet Oncol
(2012) - et al.
Patient versus clinician symptom reporting using the National Cancer Institute Common Terminology Criteria for Adverse Events: results of a questionnaire-based study
Lancet Oncol
(2006) - et al.
Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer
N Engl J Med
(2005) - et al.
Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer
N Engl J Med
(2005) - et al.
Four-year follow-up of trastuzumab plus adjuvant chemotherapy for operable human epidermal growth factor receptor 2-positive breast cancer: Joint analysis of data from NCCTG N9831 and NSABP B-31
J Clin Oncol
(2011) - et al.
Sequential versus concurrent trastuzumab in adjuvant chemotherapy for breast cancer
J Clin Oncol
(2011) - et al.
2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer (HERA): an open-label, randomised controlled trial
Lancet
(2013) - et al.
Trastuzumab plus adjuvant chemotherapy for HER2-positive breast cancer: Final planned joint analysis of overall survival (OS) from NSABP B-31 and NCCTG N9831
Cancer Res
(2012)
Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2
N Engl J Med
Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group
J Clin Oncol
Cited by (176)
Subcutaneous injection of trastuzumab into the thigh versus abdominal wall in patients with HER2-positive early breast cancer: Pharmacokinetic, safety and patients' preference - Substudy of the randomised phase III GAIN-2 study
2022, BreastCitation Excerpt :The study reported non-inferiority on pCR rates, comparable pharmacokinetics (PK) and safety results. Other studies support these findings on comparable efficacy and safety for patients with HER2-positive early [9–11] and metastatic disease [12,13]. The reported advantages of s.c. over i.v. administration are shorter treatment times of about 5 min versus 30–90 min, a reduced use of health care resources, an increased convenience for patients, all of which lead to a greater patient preference [10,12,13].