Background

In the HannaH study (NCT00950300), a 600 mg fixed dose of subcutaneous (SC) trastuzumab, administered via handheld syringe, was shown to have noninferior efficacy and comparable pharmacokinetic and safety profiles to the intravenous (IV) formulation for the (neo)adjuvant treatment of HER2-positive early breast cancer. Cohort 1 of the ongoing, randomized, multicenter, international, crossover PrefHer study (NCT01401166) showed that an overwhelming 92% of patients preferred SC trastuzumab via single-use injection device to conventional IV administration. The objective of the current analysis was to assess patient preferences for SC or IV trastuzumab in Cohort 2 of PrefHer, an independently assessed cohort in which SC trastuzumab was administered via handheld syringe.

Methods

After completing (neo)adjuvant chemotherapy, patients were randomized to receive 4 cycles of SC trastuzumab (fixed dose of 600 mg) followed by 4 cycles of IV trastuzumab (8 mg/kg→6 mg/kg) or the reverse sequence (the crossover period) as part of their adjuvant trastuzumab therapy. The primary endpoint was the proportion of patients indicating an overall preference for SC versus IV trastuzumab, assessed using a two-sided test against the null hypothesis of 65% preference for SC.

Prior to randomization and again at the end of the crossover period, experienced interviewers conducted telephone interviews with patients. Information on factors potentially influencing preferences, including type of venous access device used and experiences during administration, was collected. After the crossover period, patients’ final preferences were elicited, along with reasons for these and the strength of them. Interviews were stringently quality-controlled to ensure impartial questioning.

Four researchers independently coded from verbatim quotes the two primary reasons patients gave for their preferences. These were reconciled and grouped into ten categories for descriptive analyses.

Adverse events (AEs) were assessed by standard methods.

Results

Two hundred and forty patients were enrolled: 231 received SC and IV trastuzumab and completed both patient interviews, and 239 received ≥1 dose of study drug. Baseline demographics/characteristics/treatment histories were generally balanced.

SC trastuzumab was preferred by 199/231 patients (86%, 95% CI 81–90%; p<0.0001); 29 preferred IV (13%, 95% CI 9–18%), and 3 had no preference (1%, 95% CI 0–4%). Of the patients who preferred SC, overall preferences were “very strong” in 144/199 (72%), “fairly strong” in 36 (18%), and “not very strong” in 19 (10%). The two primary categories for SC preference were: i) time saving and ii) less pain/discomfort.

AEs were reported in 77% of patients during the crossover period (69% mild, 36% moderate, 8% severe, 0% life-threatening/fatal, 1% serious). Overall safety was comparable with the known IV profile in early breast cancer.

Summary

As with Cohort 1, patients in Cohort 2 of the PrefHer study overwhelmingly preferred SC over IV trastuzumab delivery. The 4 cycles of SC trastuzumab and 4 of IV were well tolerated. SC trastuzumab is therefore an important option in the treatment of HER2-positive early breast cancer.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-12-11.