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 . 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 
*Unrelated to HER2 treatment
1. Tan AR, et al. PD4-07. SABCS 2019.
« Palbociclib not statistically superior to capecitabine in PFS Next Article
Sensory peripheral neuropathy after taxane treatment is not uncommon »
Table of Contents: SABCS 2019
Screening, Detection, and Diagnosis
Phase 2 Trial Update
Phase 3 Trial Update
Long-Term Study Results
Triple-Negative Breast Cancer
HER2-Positive Breast Cancer
Any cookies that may not be particularly necessary for the website to function and is used specifically to collect user personal data via analytics, ads, other embedded contents are termed as non-necessary cookies. It is mandatory to procure user consent prior to running these cookies on your website.