Pharmacokinetics of Subcutaneous HER2 Therapy Noninferior in BC

Commentary
Video

Rebecca A. Shatsky, MD, discusses the outcomes of the phase 3 FeDeriCa study of subcutaneous trastuzumab and pertuzumab in patients with HER2-positive 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.

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Rebecca A. Shatsky, MD, an expert on breast cancer
Rebecca A. Shatsky, MD, an expert on breast cancer
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