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FDA Approves Subcutaneous Trastuzumab Formulation for HER2+ Breast Cancer

Gina Columbus @ginacolumbusonc
Published: Thursday, Feb 28, 2019

The FDA has approved subcutaneous use of trastuzumab (Herceptin) and hyaluronidase-oysk injection (Herceptin Hylecta) in combination with chemotherapy for the treatment of select patients with HER2-positive early breast cancer, in combination with paclitaxel in patients with metastatic HER2-positive breast cancer as a frontline treatment, and alone for patients with metastatic disease who have received at least 1 prior chemotherapy regimen.1,2

The approval is based on findings from the HannaH (NCT00950300) and SafeHER (NCT01566721) studies, in which Herceptin Hylecta demonstrated comparable rates of efficacy and safety compared with the standard intravenous (IV) use of trastuzumab, as well as the PrefHER trial (NCT01401166), which suggested a patient preference for the subcutaneous regimen.

"Over the past 20 years, Herceptin has significantly advanced treatment of HER2-positive breast cancer,” said Sandra Horning, MD, chief medical officer and head of Global Product Development, Genentech (Roche), the manufacturer of trastuzumab, in 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 formulation is a combination of trastuzumab and recombinant human hyaluronidase PH20, which is an endoglycosidase. The recommended dose of Herceptin Hylecta is 600 mg/10,000 units—identified as 600 mg trastuzumab and 10,000 units hyaluronidase—given subcutaneously over approximately 2 to 5 minutes once every 3 weeks. Standard IV trastuzumab is administered over 30 to 90 minutes. The regimen is indicated for patients whose cancer has not spread into the lymph nodes, needs to be estrogen receptor/progesterone receptor negative, or have 1 high-risk feature—identified as tumor size greater than 2 cm, is younger than 35 years of age, and a grade 2 or 3 tumor.

In the randomized HannaH study, 596 patients with HER2-positive operable or locally advanced breast cancer, including inflammatory breast cancer, received 8 cycles of either Herceptin Hylecta or IV trastuzumab concurrently with chemotherapy, followed by surgery and continued therapy with either Herceptin Hylecta or IV trastuzumab for an additional 10 cycles. The co-primary endpoints were pathologic complete response (pCR) and pharmacokinetics.

Results showed that the 45.4% pCR rate with Herceptin Hylecta (n = 118; 95% CI, 39.2%-51.7%) was similar to the 40.7% pCR rate in the IV trastuzumab arm (n = 107; 95% CI, 34.7%-46.9%; 95% CI for difference in pCR, -4.0-13.4), demonstrating noninferior levels in pharmacokinetics and noninferior clinical efficacy. Additionally, the mean level of trastuzumab in the blood before the eighth dosing cycle was 78.7 mcg/mL compared with 57.8 mcg/mL for IV trastuzumab, leading to a geometric mean ratio of 1.3 (90% CI, 1.2-1.4).

In the prospective, two-cohort, nonrandomized, international, open-label SafeHER trial, investigators evaluated the safety and tolerability of Herceptin Hylecta with chemotherapy in 1864 patients with HER2-positive breast cancer. Patients received a fixed dose of 600 mg of Herceptin Hylecta every 3 weeks for 18 cycles. The novel formulation was given either sequentially with chemotherapy, concurrently with chemotherapy, or without adjuvant chemotherapy, or in combination with neoadjuvant chemotherapy followed by trastuzumab.

Findings showed that there were no safety signals with Herceptin Hylecta and the safety profile was consistent with what was been previously associated with standard trastuzumab. The most common adverse events observed in ≥10% of patients were fatigue, arthralgia, diarrhea, injection site reaction, upper respiratory tract infection, rash, myalgia, nausea, headache, edema, flushing, pyrexia, cough, and pain in extremity.

Moreover, the PrefHER study was a patient-preference trial of 240 patients who received adjuvant Herceptin Hylecta followed by IV trastuzumab, or vice versa. Results showed that 86% of patients on the trial preferred the subcutaneous regimen versus standard IV trastuzumab (13%); 1% of patients had no preference. The most common reason for preferring Herceptin Hylecta was time savings (179/231); those who preferred the standard IV regimen reportedly did so due to fewer local injection reactions.

The FDA previously approved IV trastuzumab for the adjuvant treatment of patients with HER2-overexpressing, node-positive or node-negative breast cancer as part of a treatment regimen consisting of doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel; with docetaxel and carboplatin; and as a single agent following multi-modality anthracycline-based therapy. It is also indicated as a single agent for patients with HER2-overexpressing breast cancer who have received one or more chemotherapy regimens for metastatic disease, or in combination with paclitaxel as a first-line treatment for patients with HER2-overexpressing metastatic breast cancer.


  1. FDA Approves New Formulation of Herceptin for Subcutaneous Use. FDA. Published February 28, 2019. Accessed February 28, 2019.
  2. FDA Approves Herceptin Hylecta for Subcutaneous Injection in Certain HER2-Positive Breast Cancers. Genentech (Roche). Published February 28, 2019. Accessed February 28, 2019.

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