The FDA’s acceptance of the BLA for the fixed-dose combination was based on findings from the phase III FeDeriCa study, which showed noninferior pharmacokinetics of Perjeta and equivalent efficacy and safety to standard IV infusions of Perjeta plus Herceptin and chemotherapy. The FeDeriCa is an international, multicenter, two-arm, randomized, open-label study evaluating the pharmacokinetics, efficacy, and safety of SC injection of the FDC of Perjeta and Herceptin in combination with chemotherapy compared with standard IV infusion of Perjeta and Herceptin in combination with chemotherapy in 500 people with HER2-positive early breast cancer (EBC) who are being treated in the neoadjuvant and adjuvant settings.
The primary endpoint of the study is minimum levels of Perjeta in the blood during a given dosing interval. Secondary endpoints include safety, minimum levels of Herceptin in the blood during a given dosing interval, and total pCR, indicating there is no tumor tissue measurable in the tissue removed at the time of surgery. The safety profile of Perjeta and Herceptin FDC was analogous with that of Perjeta and Herceptin administered IV.
The FeDeriCa study met its primary endpoint, with SC administration of the FDC showing noninferior levels of Perjeta in the blood during a given dosing interval compared with IV administration of Perjeta. A secondary endpoint of the noninferior dosing interval of Herceptin was also met. A noninferiority endpoint was chosen for the study to ensure that individuals were receiving appropriate dosing with Perjeta and Herceptin compared with the established IV doses at the same treatment intervals. Moreover, rates of total pathological complete response (pCR), another secondary endpoint, were comparable between the treatment arms. 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 detected, including no significant variation in cardiac toxicity. The most common adverse events in both arms were alopecia, nausea, diarrhea, and anemia.
In previous studies of other SC formulations, SC administration was been demonstrated to be fervently favored by the majority of patients compared with IV administration of the same medicine, with the most frequent reason being that administration required less time in the clinic. The manufacturer reports SC administration of the FDC requires an estimated 8 minutes for the initial loading dose and nearly 5 minutes for each subsequent maintenance dose. This is compared with approximately 150 minutes for infusion of a loading dose of Perjeta and Herceptin using the standard IV formulations, and between 60 and 150 minutes for subsequent maintenance infusions of the two agents.