Pharmaceutical Business review

Roche’s fixed-dose subcutaneous combination of Perjeta and Herceptin comparable to intravenous formulations in people with HER2-positive breast cancer

Image: Site Roche Basel. Photo: courtesy of F. Hoffmann-La Roche Ltd.

These new data, from a primary analysis of the FeDeriCa study, will be presented in a spotlight session at 07.00 CST today at the 2019 San Antonio Breast Cancer Symposium (SABCS) in Texas, US (Abstract #PD4-07).

SC administration of the FDC takes approximately eight minutes for the initial loading dose and approximately five minutes for each subsequent maintenance dose. This is compared to approximately 150 minutes for infusion of a loading dose of Perjeta and Herceptin using the standard IV formulations, and between 60 to150 minutes for subsequent maintenance infusions of the two medicines.

“This fixed-dose subcutaneous combination has the potential to provide a quicker and less invasive method of administration for people with HER2-positive breast cancer being treated with Perjeta and Herceptin,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “This is the first time that we have brought together two of our targeted antibodies as a single subcutaneous injection that can be administered in just minutes.”

The FeDeriCa study met its primary endpoint, with SC administration of the FDC showing non-inferior levels of Perjeta in the blood during a given dosing interval (Ctrough) when compared to IV administration of Perjeta. The geometric mean ratio (GMR; a type of average used when assessing pharmacokinetics) for the primary endpoint was 1.22 (90% CI: 1.14 to 1.31), with the lower limit of the 90% CI of the GMR=1.14≥0.80 (the pre-specified non-inferiority margin). A secondary endpoint of non-inferior Ctrough of Herceptin was also met, with blood concentrations for people receiving the FDC non-inferior to those receiving IV Herceptin (GMR=1.33 [90% CI: 1.24 to 1.43]; lower limit of 90% CI of GMR=1.24≥0.80). A non-inferiority endpoint was chosen for the study to ensure that people were receiving sufficient dosing with Perjeta and Herceptin as compared to the established IV doses at the same treatment intervals. In addition, rates of total pathological complete response (pCR), a secondary endpoint, were comparable between the treatment arms, with 59.7% of patients receiving the FDC and 59.5% of patients treated with IV Perjeta and Herceptin achieving a total pCR – a difference of 0.15% (95% CI: -8.67 to 8.97).

The safety profile of the FDC in combination with chemotherapy was comparable to that of IV administration of Perjeta plus Herceptin 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, diarrhoea and anaemia.1

In previous studies, SC administration has been shown to be strongly preferred by the majority of patients compared to IV administration of the same medicine, with the most common reason being that administration required less time in the clinic.5 Roche is currently investigating patient preference for SC administration of the FDC compared to standard IV administration of Perjeta and Herceptin in people with HER2-positive eBC in the PHranceSCa study. Interim results of this phase II study will be presented at a future medical meeting.

Source: Company Press Release