FDA Approves Phesgo for Injection to Treat Adults with HER2+ Breast Cancer

The FDA has granted approval to phesgo – a combination of pertuzumab (Perjeta), trastuzumab (Herceptin), and hyaluronidase-zzxf – for injection under the skin to treat adult patients with HER2-positive breast cancer that has spread to other parts of the body, and for treatment of adult patients with early-stage disease.¹

Patients should be selected for this treatment based on an FDA-approved companion diagnostic test. Importantly, phesgo is initially used in combination with chemotherapy, though it could continue to be administered at home by a qualified healthcare professional once the chemotherapy regimen is finished.

Phesgo contains a fixed-dose combination of pertuzumab and trastuzumab with hyaluronidase for injection under the skin. The therapeutic components in the injection are the same as those found in FDA-approved intravenous (IV) pertuzumab and IV trastuzumab.

“Currently, most patients with HER2-positive breast cancer receive trastuzumab and pertuzumab at infusion centers,” Richard Padzur, 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, said in a press release. “With a new administration route, phesgo offers an out-patient option for patients to receive trastuzumab and pertuzumab.”

“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,” Padzur continued. “This application was approved about 4 months ahead of the FDA goal date.”

The FDA approval was based on results from the international, multi-center, two-arm, randomized, open-label, pivotal phase 3 FeDeriCa study.² The study evaluated the pharmacokinetics, efficacy, and safety of subcutaneous injection of phesgo in combination with chemotherapy, compared with standard IV infusions of pertuzumab and trastuzumab (Herceptin) in combination with chemotherapy, in 500 individuals with HER2-positive early breast cancer treated in the neoadjuvant and adjuvant settings.

The primary endpoint of the study was minimum levels of pertuzumab in the blood during a given dosing interval (Ctrough), when compared to IV administration of pertuzumab. Secondary endpoints included safety, minimum levels of trastuzumab in the blood during a given dosing interval (Ctrough), and total pathological complete response. Data from the FeDeriCa study were presented at the San Antonio Breast Cancer Symposium in December 2019.

The study met its primary endpoint of non-inferior levels of pertuzumab in the blood. The geometric mean ratio (GMR) for the primary endpoint was 1.22 (90% CI, 1.14-1.31), with the lower limit of the 90% CI of the GMR = 1.14 ≥ 0.80 (the pre-specified non-inferiority margin). In addition, the secondary endpoint of non-inferior levels of trastuzumab was also met, with blood concentrations for people receiving the fixed-dose combination non-inferior to those receiving IV trastuzumab (GMR, 1.33; 90% CI, 1.24-1.43]; lower limit of 90% CI of GMR = 1.24 ≥ 0.80). Notably, a non-inferiority endpoint was chosen for the study to ensure that participants were receiving sufficient dosing with pertuzumab and trastuzumab as compared to the established IV doses at the same treatment intervals.

The safety profile of phesgo with chemotherapy was comparable to IV administration of pertuzumab plus trastuzumab and chemotherapy, and no new safety signals were identified, including no meaningful difference in cardiac toxicity. The most common adverse events in both arms were alopecia, nausea, diarrhea and anemia.

The prescribing information for phesgo includes a boxed warning to advise health care professionals and patients about the risk of potential heart failure, fetal harm, and lung toxicity. The FDA indicated that healthcare professionals should use similar monitoring parameters as those already used with IV pertuzumab and IV trastuzumab.

References:

1. FDA. FDA Approves Breast Cancer Treatment That Can Be Administered At Home By Health Care Professional. FDA website. Published June 29, 2020. fda.gov/news-events/press-announcements/fda-approves-breast-cancer-treatment-can-be-administered-home-health-care-professional. Accessed June 29, 2020.

2. FDA approves Roche’s Phesgo (fixed-dose combination of Perjeta and Herceptin for subcutaneous injection) for HER2-positive breast cancer [news release]. Basel. Published June 29, 2020. globenewswire.com/news-release/2020/06/29/2054917/0/en/FDA-approves-Roche-s-Phesgo-fixed-dose-combination-of-Perjeta-and-Herceptin-for-subcutaneous-injection-for-HER2-positive-breast-cancer.html. Accessed June 29, 2020.