WASHINGTON — The FDA approved a subcutaneous version of trastuzumab (Herceptin) for treating HER2-positive breast cancer on Thursday.
Two randomized trials confirmed the safety and efficacy of the new formulation, which combines the anti-HER2 targeted agent with hyaluronidase, an endoglycosidase, and will be branded Herceptin Hylecta.
In the HannaH trial, 596 operable, HER2-positive breast cancer patients with locally advanced or inflammatory disease were randomized to 8 cycles of chemotherapy plus either subcutaneous or intravenous trastuzumab. Following surgery, they received another 10 cycles of their respective trastuzumab therapy.
The study met both primary endpoints, demonstrating that subcutaneous trastuzumab’s pharmacokinetics and rates of pathological complete response (pCR) were noninferior to standard IV therapy. Rates of pCR were 45.4% in the subcutaneous arm compared with 40.7% in the IV arm (4.7% difference, 95% CI -4.0% to 13.4%).
Adverse events (AEs) between the two formulations were generally similar in this study, but serious AEs occurred with more frequency in the subcutaneous group (21.0% vs 12.0%), driven mostly by increased rates of infections and infestations (8.1% vs 4.4%).
A second study, SafeHER, was a prospective, multinational, open-label trial that confirmed the safety and tolerability of subcutaneous trastuzumab in 1,864 HER2-positive breast cancer patients treated every 3 weeks for 18 cycles.
The most common AEs (≥10%) were arthralgia, cough, diarrhea, edema, fatigue, flushing, headache, injection site reactions, myalgia, nausea, pain in the extremities, pyrexia, rash, and upper respiratory tract infections.
A third study, PrefHER, examined patient preference. In it, 240 patients were randomized to subcutaneous trastuzumab followed by the IV formulation, or vice versa. Following treatment, 86% stated that they preferred the subcutaneous version, 13% the IV version, and 1% had no preference. As the subcutaneous formulation takes about 2 to 5 minutes to administer, time savings was the most common reason for preference over the IV version, which can take from 30 to 90 minutes. Those preferring the IV version cited injection site reactions as their reason.
The recommended dose of the new treatment is 600 mg trastuzumab and 10,000 units hyaluronidase administered subcutaneously every 3 weeks.