Dr Hafez on the Design of the FeDeriCa Trial in HER2+ Early Breast Cancer

Maria Hafez, MD, assistant professor, breast and sarcoma medical oncologist, director, Clinical Breast Cancer Research, Sidney Kimmel Medical College, Thomas Jefferson University, discusses the rationale and design of the phase 3 FeDeriCa trial (NCT03493854) in patients with HER2-positive early breast cancer, as well as key outcomes from this trial.

The randomized, multicenter, open-label, noninferiority FeDeriCa trial investigated the efficacy, safety, and pharmacokinetics of administering a fixed-dose, subcutaneous formulation of pertuzumab (Perjeta) in combination with trastuzumab (Herceptin) and chemotherapy vs standard intravenous (IV) pertuzumab plus trastuzumab and chemotherapy in the neoadjuvant setting in patients with HER2-positive early breast cancer. The chemotherapy regimen consisted of investigator’s choice of anthracycline- or non-anthracycline–based treatments, either paclitaxel or docetaxel, Hafez says. Following neoadjuvant therapy, patients underwent surgery, after which they continued to receive pertuzumab plus trastuzumab and chemotherapy for 1 year in subcutaneous or IV formulations as they had in the neoadjuvant setting.

The primary end point of FeDeriCa was the noninferiority of pertuzumab trough serum concentration (C_trough) levels between the 2 arms during cycle 7, which informed the pharmacological assessment of these regimens, Hafez explains. Key secondary end points included the trastuzumab C_trough levels between cycles 7 and 8, Hafez notes. Pathologic complete response (pCR) was a key clinical efficacy outcome, Hafez continues.

The primary and secondary end points were comparable between the 2 arms, and no statistically significant differences in C_trough levels emerged between the 2 formulations, Hafez emphasizes. Furthermore, the pharmacokinetic steady states and pCR rates were comparable between the 2 arms, according to Hafez. Notably, the toxicity profiles between the subcutaneous and IV formulations did not significantly differ, Hafez notes, although patients in the subcutaneous arm had a shorter duration of treatment than those in the IV arm. This indicates that the subcutaneous formulation may be more convenient for patients to receive. The duration of treatment with the subcutaneous regimen was approximately 5 to 7 minutes vs approximately 2 hours with the IV regimen, Hafez concludes.