Subcutaneous Regimen Shows Noninferiority to Intravenous in HER2+ Breast Cancer

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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

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

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

William J. Gradishar, MD, professor of medicine (Hematology and Oncology), Betsy Bramsen Professor of Breast Oncology, and chief of hematology and oncology in the Department of Medicine at the Feinberg School of Medicine at Northwestern University, discusses the design and results of a study of intravenous (IV) versus subcutaneous pertuzumab (Perjeta) and trastuzumab (Herceptin) in patients with HER2-positive breast cancer.

In the phase 3 randomized FeDeriCa trial (NCT03493854), 500 patients with HER2-positive breast cancer received standard neoadjuvant chemotherapy plus IV pertuzumab and trastuzumab, or chemotherapy plus subcutaneous injection of pertuzumab, trastuzumab, and hyaluronidase-zzxf (Phesgo) every 3 weeks. Patients received 4 cycles of treatment before surgery and 14 cycles following surgery.

The subcutaneous injection demonstrated non-inferiority based on analysis of cycle 7 pertuzumab serum C_trough concentration in each arm, reaching the primary end point of the lower bound of the geometric mean ratio being 0.8 or higher. The geometric mean ratio for the subcutaneous group versus the IV group was 1.22 (90% CI, 1.14-1.31). According to Gradishar, the pathological complete response (pCR) rate was 59.7% in the subcutaneous group and 59.5% in the IV group, making them roughly identical.

The toxicity profile also did not show differences between the groups, Gradishar says, concluding that the subcutaneous injection of pertuzumab and trastuzumab is equivalent to the IV form in tolerability and efficacy.

TRANSCRIPTION:

0:08 | So this was a neoadjuvant chemotherapy trial that basically looked at the use of a standard chemotherapy regimen preoperatively that was anthracycline or taxane-based with or without IV pertuzumab and trastuzumab, or the same chemotherapy option with subcutaneous pertuzumab and trastuzumab. And after surgery, patients were continued on the same HER2-directed therapy [that] they're given IV or subcutaneously. What was demonstrated in the trial is the pCR rate was exactly the same; whether you got IV or subcutaneous, it’s roughly around 60%. And the toxicity profile was no different between the 2 treatment arms.

Of course, if you look at things like, "How long did the patient require the infusion time?" In other words, the infusion time with the HER2-directed therapy was markedly less if you're getting a subcutaneous shot compared to an IV preparation of the same medication. So, on balance, it's equal efficacy, equal toxicity, and obviously shorter time in clinic to receive those particular medications.