FDA Approves Subcutaneous Herceptin Formulation for HER2-positive Breast Cancer

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

The approval is based on findings from the HannaH and SafeHER studies, in which Herceptin Hylecta demonstrated comparable rates of efficacy and safety compared with the standard intravenous (IV) use of Herceptin, as well as the PrefHER trial, 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, M.D., chief medical officer and head of Global Product Development, Genentech (Roche), the manufacturer of Herceptin, 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 Herceptin 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 Herceptin and 10,000 units Herceptin Hylecta—given subcutaneously over approximately two to five minutes once every three weeks. Standard IV Herceptin 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 one high-risk feature.

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

Results showed that the 45.4 percent pCR rate with Herceptin Hylecta (118 patients; 95 percent CI, 39.2-51.7 percent) was similar to the 40.7 percent pCR rate in the IV Herceptin arm (107 patients; 95 percent CI, 34.7-46.9 percent; 95 percent CI for difference in pCR, -4.0-13.4), demonstrating noninferior levels in pharmacokinetics and noninferior clinical efficacy. Additionally, the mean level of Herceptin in the blood before the eighth dosing cycle was 78.7 mcg/mL compared with 57.8 mcg/mL for IV Herceptin, leading to a geometric mean ratio of 1.3 (90 percent 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 1,864 patients with HER2-positive breast cancer. Patients received a fixed dose of 600 mg of Herceptin Hylecta every three 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 Herceptin.

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 Herceptin. The most common adverse events observed in ≥10 percent 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 Herceptin, or vice versa. Results showed that 86 percent of patients on the trial preferred the subcutaneous regimen versus standard IV Herceptin (13 percent); 1 percent 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.

This article originally appeared on OncLive as, "FDA Approves Subcutaneous Trastuzumab Formulation for HER2+ Breast Cancer".