Women with HER2-positive early breast cancer favor subcutaneous over intravenous (IV) administration of trastuzumab (Herceptin), according to the results of the PrefHer study.
Xavier Pivot, MD, with CHU Jean Minjoz in Besançon, France, and coworkers elsewhere randomized subjects to receive four cycles of 600-mg fixed-dose subcutaneous adjuvant trastuzumab administered via a single-use injection device or handheld syringe followed by four cycles of IV trastuzumab, or the reverse sequence. Treatment regimens containing IV trastuzumab are the standard of care for patients with HER2-positive breast cancer.
In the 596-patient, phase III HANNAH trial, subcutaneous trastuzumab demonstrated a pharmacokinetic profile and efficacy that was noninferior to IV administration, with a similar safety profile.
The PrefHer study included women with HER2-positive primary invasive breast adenocarcinoma and no evidence of residual, locally recurrent, or metastatic disease after completion of surgery and chemotherapy.
Study participants were either trastuzumab-naïve (de novo group) or had already received IV trastuzumab as part of a concurrent or sequential regimen following neoadjuvant or adjuvant chemotherapy (non-de novo group). The non-de novo patients had to have had at least eight of 18 planned thrice-weekly trastuzumab cycles left to complete prior to enrollment.
The researchers noted that subcutaneous trastuzumab administration has an injection time of less than 5 minutes versus 30 to 90 minutes for IV administration, which is important in long-term or single-agent trastuzumab therapy. Additional advantages include decreased use of both hospital resources and the services of healthcare professionals.
Subcutaneous trastuzumab was recently approved in Europe for the treatment of women with HER2-positive early breast cancer.
The evaluable intent-totreat population included 117 patients who received subcutaneous trastuzumab followed by IV trastuzumab and 119 patients who received IV trastuzumab followed by subcutaneous trastuzumab.
Patient preferences for route of administration were determined by telephone interviews.
The two treatment groups were similar with respect to demographics, characteristics, and treatment history.
Overall, 216 patients (91.5%) preferred subcutaneous trastuzumab administration (95% CI, 87.2-94.7; P
<.0001), 16 patients (6.8%; 95% CI, 3.9-10.8) favored IV delivery, and 4 patients (1.7%; 95% CI, 0.5-4.3) reported no preference.
Further analysis revealed a preference for subcutaneous trastuzumab irrespective of trastuzumab therapy before enrollment (54 of 57 [94.7%; 95% CI, 85.4-98.9] in the de novo group and 162 of 179 [90.5%; 95% CI, 85.2-94.4] in the non-de novo group).
Clinician-reported adverse events occurred in 58% of patients during the pooled subcutaneous periods versus 44% of patients during the pooled IV periods.
However, this pattern was not demonstrated in patientreported events, in which case decreased pain or discomfort was the second most common reason given for preference of subcutaneous administration.
The main reason that patients cited for preferring the subcutaneous route of administration was that it saved time.
Pivot et al noted that the study’s main strengths “lie with its prospective randomized design and the primary analysis.”
In addition, patients were asked about their preference by an independent interviewer “in a comprehensive, quality-controlled interview process.” This method is better than other popular methods of assessing patient preference, including retrospective assessments, questionnaires completed by the treating institution, and healthcare professional–based preference reporting, they said.
The authors concluded that combined data from the PrefHer and HANNAH studies “suggest that a fixed dose of subcutaneous trastuzumab every 3 weeks is a validated, well-tolerated, and preferred option of patients for the treatment of HER2-positive breast cancer.”
Pivot X, Gligorov J, Müller V, et al. Preference for subcutaneous or intravenous administration of trastuzumab in patients with HER2-positive early breast cancer (PrefHer): an open-label randomised study. Lancet Oncol. 2013;14(10):962-970.