(ChemotherapyAdvisor) – Neoadjuvant subcutaneous (SC) trastuzumab “offers a valid treatment alternative” to intravenous (IV) administration in patients with HER2-positive, clinical stage I-III breast cancer, according to results of the phase 3 open-label randomized HannaH study published online first in The Lancet Oncology August 8.
“Our study shows that subcutaneously delivered trastuzumab offers a valid alternative to existing intravenously delivered treatments,” said Gustavo Ismael, MD, of the Amaral Carvalho Hospital in Brazil. “The shortened duration of administration with subcutaneous trastuzumab has the potential to save time for patients, physicians and nursing staff.”
The trial randomly assigned patients to 4 cycles of neoadjuvant chemotherapy—docetaxel 75mg/m² followed by 4 cycles of 5-fluorouracil 500mg/m², epirubicin 75mg/m², and cyclophosphamide 500mg/m² every 3 weeks—concurrently with trastuzumab every 3 weeks either IV (8mg/kg loading dose, 6mg/kg maintenance dose; n=299) or SC (fixed dose of 600mg; n=297) to compare the pharmacokinetic profile, efficacy, and safety of the two formulations. Following surgery, trastuzumab was administered to complete 1 year of treatment.
The co-primary end points were serum trough concentration (Ctrough) at predose cycle 8 before surgery and pathological complete response (pCR), analyzed in the per-protocol population.
Presurgery, geometric mean Ctrough was 51.8 μg/mL in the IV arm and 69.0 μg/mL in the SC arm. The geometric mean ratio of Ctrough SC to Ctrough IV was 1.33 (90% CI, 1.24–1.44). A total of 107 of 263 patients (40.7%) in the IV arm and 118 of 260 (45.4%) in the SC arm achieved a pCR, for a 4.7% (95% CI, -4·0–13·4) difference between groups. “Thus, subcutaneous trastuzumab was noninferior to intravenous trastuzumab for both co-primary end points,” the investigators reported.
The most common grade 3-5 adverse events (AEs) were neutropenia (99 of 298 patients [33.2%] in the IV group vs 86 of 297 [29.0%] in the SC group), leukopenia (17 [5.7%] vs 12 [4.0%]), and febrile neutropenia (10 [3.4%] vs 17 [5.7%]).
Serious AEs occurred in 21% of patients in the SC group and in 12% in the IV group. “The difference was mainly attributable to infections and infestations (24 [8.1%] in the subcutaneous group vs 13 [4.4%] in the intravenous group),” they wrote. The 4 AEs that led to death all occurred during the neoadjuvant phase, 1 in the IV arm and 3 in the SC arm. “Of these, 2—both in the subcutaneous group—were deemed to be treatment related,” they reported.
In a linked Comment, Javier Cortes, MD, of the Vall d´Hebron Institute of Oncology in Spain, noted that “the ability to deliver the drug in about 5 minutes without the need to secure intravenous access makes subcutaneous treatment more convenient. In addition to time savings, once the drug can be administered at home, patients will be able to continue their lives with less hospital dependence, which is an important psychological aspect. This treatment will also save resources in terms of nurses and cleaning in already crowded hospitals.”