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Subcutaneous pertuzumab + trastuzumab non-inferior to the IV combination

SABCS 2019
Phase 3, FeDeriCa

A new fixed-dose combination of subcutaneous (SC) of pertuzumab + trastuzumab demonstrated non-inferiority compared with the same regimen which was administered intravenously (IV), with comparable efficacy and safety. This new formulation offers patients with human epidermal growth factor 2 (HER2)-positive breast cancer a faster and simpler method of pertuzumab + trastuzumab administration.

Tan et al. presented the first results from the FeDeriCa study which was designed to assess the pharmacokinetics, efficacy, and safety of a novel SC fixed-dose combination of pertuzumab + trastuzumab compared with IV trastuzumab + pertuzumab in patients with HER2-positive early breast cancer in the neoadjuvant-adjuvant setting [1]. The new SC formulation was developed using recombinant human hyaluronidase in one vial and is administered into the thigh over 5-8 minutes. Eligible patients had centrally confirmed HER2-positive invasive breast cancer (tumour >2 cm, or node-positive disease; stage II-IIIC). A total of 500 patients were randomised 1:1 to receive 8 cycles of chemotherapy in the neoadjuvant setting with trastuzumab + pertuzumab IV (Arm A) or chemotherapy per Arm A + fixed-dose combination pertuzumab + trastuzumab SC (Arm B) administered every 3 weeks during cycles 5-8. Chemotherapy was investigator’s choice of either 4 cycles of dose-dense doxorubicin + cyclophosphamide every 2 weeks followed by 4 cycles of weekly paclitaxel, or 4 cycles of doxorubicin + cyclophosphamide every 3 weeks followed by 4 cycles of docetaxel every 3 weeks. Post-surgery, patients continued anti-HER2 treatment per randomisation to complete 18 cycles. The primary objective of the study was non-inferiority of the pre-dose cycle 8 pertuzumab serum trough concentration (Ctrough) within the pertuzumab + trastuzumab fixed-dose combination versus pertuzumab (non-inferiority margin ≥0.8). Key secondary objectives were non-inferiority of pre-dose cycle 8 trastuzumab Ctrough within the pertuzumab + trastuzumab fixed-dose combination versus trastuzumab IV, total pathologic complete response in the breast and axilla (ypT0/is, ypN0; tpCR), and safety.

At clinical cutoff (April 2019), 96.0% of patients in Arm A and 94.4% in Arm B completed the neoadjuvant treatment phase. Baseline patient demographics and disease characteristics were well balanced between arms. The study met its primary endpoint: pertuzumab geometric mean ratio was 1.22 (90% CI 1.14-1.31) with the lower limit of the 90% CI being above the prespecified non-inferiority margin of 0.8. Trastuzumab geometric mean ratio was 1.33 (90% CI 1.24-1.43), also meeting the non-inferiority criteria. The total pathologic complete response rates were comparable between arms (59.5%; 95% CI 53.2-65.6 in Arm A and 59.7%; 95% CI 53.3-65.8 in Arm B) and were similar to other pertuzumab + trastuzumab + chemotherapy trials. Overall safety, including cardiac safety, was comparable between arms (see Table).

Table. Overview of safety results from FeDeriCa [1]

*Unrelated to HER2 treatment

1. Tan AR, et al. PD4-07. SABCS 2019.

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