FDA Approves Subcutaneous Phesgo Regimen in HER2+ Early Breast Cancer

"The FDA approval of Phesgo reflects our commitment to improving outcomes for the many people living with HER2-positive breast cancer."

The FDA granted approval to the combination of pertuzumab, trastuzumab, and hyaluronidase-zzxf (Phesgo) by subcutaneous injection as treatment of patients with HER2-positive breast cancer that has spread to other parts of the body, as well as for the treatment of adult patients with early HER2-positive breast cancer. This is the first regimen containing 2 monoclonal antibodies that is approved for administration subcutaneously. The approval was also 4 months ahead of the target action date.1,2,3

"The FDA approval of Phesgo reflects our commitment to improving outcomes for the many people living with HER2-positive breast cancer," said Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development, Genentech, Inc. "Phesgo offers a treatment administration that supports the needs and preferences of individual patients, and helps to meet the increasing demand across the healthcare system for faster and more flexible treatment options."

A non-inferiority study (FeDeriCa, NCT03493854) of Phesgo compared with intravenous (IV) pertuzumab and IV trastuzumab served as the basis for the FDA approval.2

In the study, subcutaneous Phesgo was found to have comparable efficacy and safety to IV pertuzumab and trastuzumab, meeting the primary end point of non-inferiority of the fixed-dose combination’s (FDC) predose cycle 8 serum Ctroughfor the pertuzumab. The mean value was 93.7 versus 78.5 µg/mL for IV pertuzumab, and the geometric means, respectively, were 88.7 and 72.4 µg/mL, achieving a geometric mean ratio (GMR) of 1.22 (90% CI, 1.14-1.31).

With trastuzumab, the noninferiority for the predose cycle 8 serum Ctroughfor the trastuzumab component of the FDC compared with IV was 62.9 compared with 48.1 (GMR, 1.33; 90% CI, 1.24-1.43).

Partial complete response rates were similar between the treatment arms at 59.7% % for FDC versus 59.5% for IV.

In a prior interview with Targeted Oncology following the presentation of these data at the 2019 San Antonio Breast Cancer Symposium (SABCS), study author Antoinette R. Tan, MD, said the key takeaways are that the pharmacokinetics of the subcutaneous fixed-dose formulation of pertuzumab was non-inferior compared to the IV counterpart, the efficacy was also nearly identical as measured by PCR rate, and the safety also was comparable, including cardiac safety.”

In the safety analysis, the most common adverse events (AEs) were similar between the treatment arms, which included alopecia, nausea, diarrhea, anemia, and asthenia. The FDA warns that in addition to the AEs, Phesgo should not be administered in pregnant women or within 7 months prior to conception as the drug may harm the fetus. The FDA also warns that in the case of anaphylaxis, patients should discontinue treatment.

“Currently, most patients with HER2-positive breast cancer receive trastuzumab and pertuzumab at infusion centers. With a new administration route, Phesgo offers an outpatient option for patients to receive trastuzumab and pertuzumab,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research. “As part of the FDA’s ongoing commitment to address the novel coronavirus pandemic, we continue to keep a strong focus on patients with cancer who constitute a vulnerable population at risk of contracting the disease. At this critical time, we continue to expedite oncology product development. This application was approved about four months ahead of the FDA goal date.”

The FeDEriCa study was designed to evaluate the pharmacokinetics, safety, and the activity of the fixed-dose combination of trastuzumab and pertuzumab subcutaneously, compared to the IV formulation of trastuzumab and pertuzumab in patients with early-stage HER2-positive breast cancer. A total of 500 subjects with early-stage breast cancer were enrolled.1,2,3

A separate phase 2 study (PHranceSCa, NCT03674112) revealed that patients with HER2-positive breast cancer prefer subcutaneous treatment to IV treatment. The rate was 85% (136 out of 160) patients.3


1. FDA approves Genentech’s Phesgo (fixed-dose combination of Perjeta and Herceptin for subcutaneous injection) for her2-positive breast cancer. Genetech, Inc. News release. June 29, 2020. Accessed June 29, 2020. https://bit.ly/3gavbEa

2. FDA approves breast cancer treatment that can be administered at home by health care professional. FDA website. News release. June 29, 2020. Accessed June 29, 2020. https://bit.ly/3glTu2n

3. Halozyme announces Roche receives FDA approval for Phesgo™ (fixed-dose combination of Perjeta® and Herceptin® for subcutaneous injection) utilizing Halozyme's Enhanze® technology for the treatment of patients with her2-positive breast cancer. Halozyme Therpeutics, Inc. News release. June 29, 2020. Accessed June 29, 2020. https://bit.ly/3dFJwqN

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