FDA Approves Subcutaneous Trastuzumab Formulation for HER2+ Breast Cancer

March 5, 2019

The US Food and Drug Administration has approved the subcutaneous administration of trastuzumab for patients with HER2-overexpressing breast cancer.

At the end of February, the US Food and Drug Administration approved the subcutaneous administration of trastuzumab, known as Herceptin Hylecta (Genentech). The therapy combines trastuzumab, a HER2/neu receptor antagonist, with a drug delivery molecule known as hyaluronidase-oysk, and is approved both alone and in combination with chemotherapy for patients with HER2-overexpressing breast cancer.

“Over the past 20 years, Herceptin has significantly advanced treatment of HER2-positive breast cancer,” said Sandra Horning, MD, chief medical officer of Genentech, according to a press release. “The approval of Herceptin Hylecta gives physicians and patients in the United States a new option to select treatment based on individual needs and preferences.”

The approval was based on results of two large trials. The HannaH trial included 596 patients with operable or locally advanced HER2-positive breast cancer; patients were randomized to receive either subcutaneous or intravenous trastuzumab concurrently with chemotherapy. All patients then underwent surgery and continued therapy with either the subcutaneous or intravenous formulations of trastuzumab for 10 cycles. In that trial, the pathologic complete response rates were similar with the two therapies, at 45.4% with Herceptin Hylecta and 40.7% with intravenous trastuzumab.

In the SafeHER trial, a total of 1,864 patients with HER2-positive breast cancer were included. In this case, all patients received the subcutaneous formulation of trastuzumab, either with sequential chemotherapy, concurrent chemotherapy, or without adjuvant chemotherapy, or in combination with neoadjuvant chemotherapy followed by further trastuzumab. This trial was designed to assess the general safety of the formulation, and no new safety signals emerged. The most common adverse events included administration-related reactions, fatigue, diarrhea, weakness, rash, and several others occurring in at least 10% of patients.

A further trial, the PrefHER study, illustrated the potential benefit of the subcutaneous injection. In that study, 121 patients with HER2-positive breast cancer received Herceptin Hylecta followed by intravenous Herceptin, and 119 patients received the two agents in the opposite sequence. In total, 86% of patients in the study preferred the subcutaneous route of administration, compared with 13% who preferred the intravenous formulation; 1% had no preference between the two. The most common reason cited for the preference of Herceptin Hylecta was time savings, while the most common reason to prefer the IV route was fewer local injection reactions.

In an editorial published upon the release of the PrefHER trial results, Jean Michel Lavoie, MD, and Karen A. Gelmon, MD, of the British Columbia Cancer Agency in Vancouver, wrote that the new formulation could help with access to care for some women with HER2-positive breast cancer.

“In the adjuvant setting, many patients from remote areas need to travel a substantial distance to access an infusion clinic for 18 cycles of treatment,” they wrote. “Subcutaneous trastuzumab can be administered closer to home by a properly trained healthcare provider, thus improving access to a cornerstone of systemic therapy for those patients.” They added that this route of administration can reduce the use of resources, including nursing, pharmacy, and others, along with the time commitment of the patient.