Pharmacokinetics of Subcutaneous HER2 Therapy Noninferior in BC

EP: 1.Subcutaneous Regimen Shows Noninferiority to Intravenous in HER2+ Breast Cancer

EP: 2.Patients Prefer Subcutaneous Regimen for HER2-Positive Breast Cancer

EP: 3.Subcutaneous Regimen Shows Non-Inferiority for HER2+ Breast Cancer

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EP: 4.Pharmacokinetics of Subcutaneous HER2 Therapy Noninferior in BC

EP: 5.Advantages of SC HER2 Therapy Over IV Administration in Breast Cancer

Rebecca A. Shatsky, MD, associate professor of medicine at UC San Diego School of Medicine, discusses the outcomes of the phase 3 FeDeriCa study (NCT03493854) of subcutaneous (SC) trastuzumab and pertuzumab (Phesgo) in patients with HER2-positive breast cancer.

The randomized, multicenter, open-label phase 3 trial investigated the SC formulation in comparison with intravenous (IV) trastuzumab (Herceptin) and pertuzumab (Perjeta). Investigators enrolled patients with operable or locally advanced HER2-positive breast cancer. Patients received neoadjuvant dose-dense doxorubicin plus cyclophosphamide for 4 cycles, followed by either docetaxel or paclitaxel. They then received the SC fixed-dose combination or IV combination of trastuzumab/pertuzumab for 4 cycles followed by surgical resection, then 14 more cycles of trastuzumab/pertuzumab.

The primary end point of the trial was noninferior pharmacokinetics of the SC method of administration. Looking at cycle 7 pertuzumab serum trough concentration, noninferiority was defined as the lower bound of the 90% CI of the geometric mean ratio being 0.8 or higher. The study found that the geometric mean ratio of pertuzumab serum trough concentration of the SC vs IV was 1.22 (90% CI, 1.14-1.31). A secondary end point, the geometric mean ratio of trastuzumab serum trough concentration at cycle 7, was 1.33 (90% CI, 1.24-1.43). The pathological complete response rate was 59.5% in the intravenous group and 59.7% in the SC group, and safety outcomes were also similar between the 2 groups.

TRANSCRIPTION:

0:08 | This trial was designed for noninferiority evaluation to look at the combination of IV pertuzumab/trastuzumab vs Phesgo to see if efficacy of Phesgo was noninferior to IV pertuzumab/trastuzumab and they looked at their primary end point was actually the pharmacokinetics of the Phesgo vs the IV pertuzumab/trastuzumab. And in the trial, they found that the pharmacokinetics were noninferior. The trial was considered noninferior if the lower limit of the 90% confidence interval was greater than or equal to 0.8. For all of the pharmacokinetic data, the lower limit of the confidence interval was actually higher than 1.0.