Intravenous pertuzumab (P IV) + intravenous trastuzumab (H IV) + chemotherapy (CT) improves outcomes in patients with HER2+ breast cancer, compared with trastuzumab + chemotherapy. A new subcutaneous (SC) fixed-dose formulation of pertuzumab + trastuzumab (for the first time combining 2 monoclonal antibodies in an SC formulation) was developed, and at SABCS 2019, the first results from FeDeriCa were reported, which was designed to assess the pharmacokinetics, efficacy, and safety of this novel SC formulation (PH-FDC) compared with H IV + P IV in patients with HER2+ early breast cancer in the neoadjuvant-adjuvant setting.1
Patients with centrally confirmed HER2+ invasive breast cancer (tumor >2 cm, or node-positive disease; stage II-IIIC) were randomized 1:1 to receive 8 cycles of CT in the neoadjuvant setting with H IV (loading dose 8 mg/kg, maintenance 6 mg/kg) + P IV (loading dose 840 mg, maintenance 420 mg) (Arm A) or CT per Arm A + PH-FDC (loading dose 1200 mg of pertuzumab SC/600 mg of trastuzumab SC, maintenance 600 mg each; Arm B) administered every 3 weeks during cycles 5 to 8. CT 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. Postsurgery, patients continued anti-HER2 treatment per randomization to complete 18 cycles.
The primary objective was noninferiority of the predose pertuzumab serum trough concentration (Ctrough) of PH-FDC versus P IV. Key secondary objectives were noninferiority of predose H Ctrough of PH-FDC versus H IV, total pathologic complete response in the breast and axilla, and safety. A total of 500 patients were randomized (252 to Arm A, 248 to Arm B) at 122 sites. The study met its primary end point in that SC PH-FDC demonstrated noninferior predose P + H Ctrough to that of P IV + H IV within prespecified pharmacokinetic parameters. PH-FDC SC had nearly identical total pathologic complete response to P + H IV (59.7% vs 59.5%, respectively). Safety was comparable between arms for overall adverse events, grade 3-5 adverse events, serious adverse events, deaths, and cardiac events.
The authors concluded that PH-FDC SC was noninferior to P + H IV based on predose cycle 8 P and H Ctrough. Efficacy and safety in the 2 arms were comparable. Overall, PH-FDC SC offers a faster, less invasive, simpler method of administration of pertuzumab + trastuzumab in patients with HER2+ breast cancer.
Reference
- Tan AR, et al. SABCS 2019. Abstract PD4-07.