HannaH Trial Results Show Comparability of Subcutaneous, Intravenous Trastuzumab

The subcutaneously administered trastuzumab contains the same monoclonal antibody as the intravenous formulation at a dose of 600 mg per 5-mL vial, plus a recombinant human hyaluronidase, to be used every 3 weeks. The hyaluronidase is used to increase the permeability of the extracellular matrix, allowing for administration of higher volumes and enhanced absorption of the drug.
Kelly Davio
July 05, 2019
In March of this year, the FDA approved a subcutaneously administered version of brand-name trastuzumab, Herceptin. The product, trastuzumab and hyaluronidase-oysk, was approved under the brand name Herceptin Hylecta.

The subcutaneously administered trastuzumab contains the same monoclonal antibody as the intravenous formulation at a dose of 600 mg per 5-mL vial, plus a recombinant human hyaluronidase, to be used every 3 weeks. The hyaluronidase is used to increase the permeability of the extracellular matrix, allowing for administration of higher volumes and enhanced absorption of the drug.

On the heels of the approval, researchers have now reported a final analysis of the HannaH trial, a phase 3 study that helped secure the FDA’s approval. In the trial 294 patients with ERBB2–positive early breast cancer were treated with 8 cycles of chemotherapy and subcutaneous trastuzumab, and 297 patients were treated with chemotherapy plus the intravenous trastuzumab. Patients then received another 10 cycles of their assigned trastuzumab in the adjuvant setting for 1 year.

Six-year event-free survival rates were 65% in both arms (hazard ratio [HR], 0.98; 95% CI, 0.74-1.29) and overall survival rates were 84% in both arms (HR, 0.94; 95% CI, 0.61-1.45).  

The incidence of adverse events (AEs) was comparable between arms, with 97.6% and 94.6% of patients reporting AEs in the subcutaneous and intravenous groups, respectively. Serious AEs were reported in 21.9% and 15.1% of patients, respectively, and the incidence of cardiac AEs was also similar, at 14.8% and 14.1%, respectively, even for patients in the lowest body-weight quartile.

These data, which support the long-term comparability in terms of efficacy and safety of the subcutaneous trastuzumab versus the intravenous option, will be welcome reassurance for patients and providers who seek to reduce the burden of chair time for lengthy infusions with trastuzumab. The newly approved subcutaneous formulation has also been shown to save on costs in other regulatory territories where the drug is already widely in use. 

For developers of intravenously administered biosimilar products, however, these results may be cause for business-related concern; in the United States, 5 biosimilars of trastuzumab have been approved (Ontruzant, Herzuma, Kanjinti, Ogivri, and Trazimera), and the first of these agents are expected to launch as early as this year. However, all of these biosimilars are in intravenous formulations, with no biosimilar subcutaneous options. It remains to be seen how deeply discounted these biosimilars will be, and whether those cost savings will be able to outweigh the benefits of a subcutaneous administration option.

Reference
Jackisch C, Stroyakovskiy D, Pivot X, et al. Subcutaneous vs intravenous trastuzumab for patients with ERBB2-positive early breast cancer: final analysis of the HannaH phase 3 randomized clinical trial. JAMA Oncol. 2019;5(5):e190339. doi: 10.1001/jamaoncol.2019.0339.

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