CHMP Recommends Approval of At-Home, Subcutaneous Trastuzumab/Pertuzumab in HER2+ Breast Cancer

At-Home, Subcutaneous Trastuzumab/Pertuzumab

in HER2+ Breast Cancer | Image Credit:

© Sebastian Kaulitzki– stock.adobe.com

The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion recommending an update to the European Union (EU) label for a fixed-dose subcutaneous combination of pertuzumab (Perjeta), trastuzumab (Herceptin), and hyaluronidase-zzxf (Phesgo) for the treatment of HER2-positive breast cancer, to include the option for administration outside of clinical settings.1

The combination regimen is already approved as a subcutaneous alternative to intravenous (IV) pertuzumab plus trastuzumab for patients with HER2-positive early-stage and metastatic breast cancer in more than 120 countries/regions based on data from the phase 3 FeDeriCa trial (NCT03493854). In FeDeriCa, treatment with the subcutaneous regimen showed similar efficacy compared with that of the IV regimen and resulted in noninferior levels of pertuzumab and trastuzumab in the blood.2

This updated recommendation is supported by data from the AL42478 expanded access study (NCT04395508), which evaluated the combination in patients with early-stage and metastatic HER2-positive breast cancer and demonstrated that at-home administration of the subcutaneous regimen by a healthcare professional was feasible, preferred by patients, and associated with no new safety signals.1

"Treatments, like [pertuzumab/ trastuzumab and hyaluronidase], that can be administered at home offer patients a more manageable option, with the potential to improve their quality of life," Sandrine Lavallé, of the European Patients Academy on Therapeutic Innovation (EUPATI), Luxembourg, stated in a news release."This reduces the burden of hospital commuting time, anxiety associated with being in a hospital infusion chair and minimizes disruption to daily life. Patient safety is paramount, requiring clear instructions, education, and support for at-home treatment."

AL42478 Study Design

The AL42478 expanded access study is a single-arm, multicenter trial evaluating the feasibility and safety of at-home administration of the subcutaneous fixed-dose combination of pertuzumab/ trastuzumab and hyaluronidase in patients with HER2-positive breast cancer.3 The primary objective of the study was to ensure continuity of HER2-targeted therapy during the COVID-19 pandemic while reducing the need for in-clinic visits.

The study enrolled female or male patients with histologically confirmed HER2-positive breast cancer who completed chemotherapy in combination with intravenous pertuzumab and trastuzumab and were currently receiving, or are planned to receive, maintenance therapy with either pertuzumab/trastuzumab/hyaluronidase-zzxf SC, or subcutaneous trastuzumab, regardless of the number of remaining treatment cycles.

HER2-positive status must have been previously confirmed and defined as immunohistochemistry 3+ and/or positive HER2 amplification by in situ hybridization, with a HER2/CEP17 ratio of 2 or more.

Additional eligibility criteria include:

• ECOG performance status of 0 to 2
• Intact skin at the intended subcutaneous injection site (thigh)
• Baseline and most recent left ventricular ejection fraction (LVEF) ≥ 50%, measured by either echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan within the prior 3 months

Under the study protocol, patients received pertuzumab/ trastuzumab and hyaluronidase at home every 3 weeks via a home health nursing provider. Treatment continued until completion of 1 year of total HER2 blockade or until criteria for discontinuation—such as disease progression, unacceptable toxicity, patient withdrawal, or physician discretion—were met.

An optional remote cardiac surveillance substudy was also available at select sites to monitor cardiac safety during home-based treatment.

“At-home treatment may help alleviate the pressure on healthcare systems through significant capacity savings. This aligns with patient preferences, as data indicate 91% favor at-home administration over in-clinic treatment,” Levi Garraway, MD, PhD, Roche’s chief medical officer and head of Global Product Development concluded in the news release.1

References

1. CHMP recommends EU label update for Roche’s Phesgo to allow administration outside of clinical setting. News Release. Roche. April 29, 2025. Accessed April 30, 2025.https://www.roche.com/media/releases/med-cor-2025-04-30
2. Tan AR, Im SA, Mattar A, et al. Fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection plus chemotherapy in HER2-positive early breast cancer (FeDeriCa): a randomised, open-label, multicentre, non-inferiority, phase 3 study. Lancet Oncol. 2021;22(1):85-97. doi:10.1016/S1470-2045(20)30536-2
3. An expanded access study to provide at home subcutaneous administration of pertuzumab and trastuzumab fixed-dose combination (ph fdc sc) for patients with her2-positive breast cancer during the Covid-19 pandemic. ClinialTrials.gov. Updated July 5, 2022. Accessed April 30, 2025.