Subcutaneous trastuzumab demonstrated a safety profile that is consistent with the known profile with intravenous administration.
Subcutaneous trastuzumab (Herceptin) demonstrated a safety profile similar to that of intravenous trastuzumab, according to findings from the final analysis of the phase 3 MetaspHER trial (NCT01810393) published in Clinical Breast Cancer.1 Of note, no new concerns related to prolonged exposure in patients with HER2-positive metastatic breast cancer emerged.
During the study treatment period (cycles 1-18), patients in the intent-to-treat (ITT) population (n = 113) who received subcutaneous trastuzumab experienced an any grade adverse effect (AE), a grade 3 or greater AE, and a serious AE at rates of 92.0%, 20.4%, and 14.2%, respectively. One patient died from biliary cholestasis which was determined to not be related to study treatment, and 2 others discontinued treatment due to AEs.1
The most common any grade AEs included asthenia (28.3%), injection site pain (26.6%), arthralgia (15.9%), and injection site erythema (15.0%). Ten patients (8.0%) experienced at least 1 cardiac AE, including 4 with more than 10% ejection fraction decrease.1
At a median overall study duration of 3.8 years (range, 0.1-4.1), patients experienced an any grade AE, a grade 3 or greater AE, and a serious AE at rates of 92.0%, 23.0%, and 16.8%, respectively, and 1 patient died from leukemia. Cardiac events were reported in 10.8% of patients, including 5 patients who experienced a decrease in left ventricle ejection fraction, with 6.2% of patients experiencing the cardiac AEs due to study treatment. Common any grade AEs included asthenia (30.1%), injection site pain (26.6%), arthralgia (15.9%), and injection site erythema (15.0%).1
MetaspHER enrolled patients with HER2-positive metastatic breast cancer who completed frontline chemotherapy with intravenous trastuzumab and achieved a response lasting over 3 years at 55 sites in France. Patients also needed to be at least 18 years of age, have an ECOG performance status of 1 or less, and have a baseline left ventricular ejection fraction above 50% over the 3 months before inclusion to be eligible for the study.1
Patients were randomly assigned to receive subcutaneous trastuzumab for 3 cycles at a fixed dose of 600 mg followed by standard intravenous trastuzumab at a dose of 6 mg/kg over a 30- to 90-minute span for 3 cycles or the reverse sequence in a crossover period which lasted from cycle 1 through 6. Patients received subcutaneous trastuzumab after the crossover period until disease progression and those who were unable to tolerate subcutaneous trastuzumab were allowed to return to intravenous administration.1
The primary end point was patient preference for subcutaneous trastuzumab vs intravenous trastuzumab at cycle 6. Secondary end points included health care professional satisfaction, safety, and quality of life by the QLQ C30 questionnaire during the crossover period.1
Previous findings from MetaspHER published in the European Journal of Cancer in 2017 showed that 79 of 92 (85.9%; 95% CI, 78.8%-93.0%; P < .001) evaluable patients in the ITT population preferred subcutaneous administration of trastuzumab, with the remaining 14.1% (95% CI, 7.0%-21.3%) preferring intravenous delivery. Additionally, health care professionals (n = 88) also said they preferred using subcutaneous trastuzumab at a rate of 63.6%, (range, 53.6%-73.7%). No significant quality-of-life differences between patients who received the 2 methods of administration were reported.2
The median age of all patients in the ITT population was 59 years (range, 35-85), the median left ventricle ejection fraction during the metastatic period was 66% (range, 51%-82%), and patients experienced a median of 5.3 years (interquartile range, 3.8-7.5) without progression following the start of frontline treatment. At baseline, most patients had an ECOG performance status of 0 (84.1%), ER-positive disease (50.4%), a CR at the end of first-line chemotherapy (55.4%), a CR at baseline (63.4%), underwent hormonal treatment (58.4%), underwent surgery of metastases (13.3%) or primary tumor (31.9%), and were not metastatic at presentation (51.3%). The baseline characteristics were generally well balanced between the 2 arms before the crossover period.1
A majority of patients were able to complete treatment through cycle 18 (81.4%). Patients primarily discontinued treatment due to disease progression (n = 7) and withdrawal of consent (n = 2). Notably, during the crossover period, 2 patients returned to treatment with intravenous trastuzumab: 1 at patient request at cycle 7 and another at cycle 9 due to an AE.1
Additionally, at a median follow-up of 45.4 months (range, 0.8-48.8), findings from the exploratory survival analysis revealed that the median progression-free survival (PFS) in the ITT population was 23.1 months (range, 4.0-48.0), with 24.8% of patients experiencing at least 1 PFS event. The 12- and 42-month PFS rates were 93.1% (range, 86.1%-96.7%) and 74.8% (range, 64.7%-82.4%), respectively. Age, performance status, baseline metastatic site, and estrogen receptor (ER) and/or progesterone receptor tumor status did not affect the risk of progression. Notably, 19.7% of patients with complete response (CR) status at screening experienced an event counting for progression compared with 34.1% of patients without a CR at screening (HR, 0.58; 95% CI, 0.29-1.12).1
At study’s end 6 patients died—3 due to disease progression, 2 due to AEs, and 1 for an unknown reason. The overall survival rate was 100% at 1 year and 94.9% (range, 88.2%-97.9%) at month 42.1