Final analysis of the FeDeriCa phase III study: long-term efficacy, safety and pharmacokinetics of the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection, plus chemotherapy, in HER2-positive early breast cancer

BACKGROUND: FeDeriCa (NCT03493854) showed that the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection (PH FDC SC) was noninferior to intravenous (IV) P and H, with comparable total pathological response rates and safety profiles when given as neoadjuvant therapy for human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (BC). We report long-term efficacy and safety. MATERIALS AND METHODS: Patients received eight neoadjuvant chemotherapy + P IV + H IV cycles or PH FDC SC every 3 weeks (cycles 5-8; 1:1 randomisation). Patients continued adjuvant HER2-targeted treatment to complete 18 cycles. RESULTS: Data cut-off was 2 June 2023, with a median follow-up of 51.4 (P + H IV arm) and 51.2 months (PH FDC SC arm). Four-year event-free rates (invasive disease-free survival, event-free survival, distant recurrence-free interval, and overall survival) were 89.6 [95% confidence interval (CI) 85.5-93.7], 88.5 (95% CI 84.4-92.5), 92.5 (95% CI 89.2-95.8) and 95.5 (95% CI 92.9-98.1) in the P + H IV arm and 88.5 (95% CI 84.3-92.7), 86.6 (95% CI 82.2-90.9), 91.9 (95% CI 88.4-95.4) and 94.1 (95% CI 91.1-97.1) in the PH FDC SC arm, respectively. No new safety signals (including cardiac safety) were observed. CONCLUSIONS: Long-term efficacy of PH FDC SC and P + H IV was comparable. Safety remained similar and consistent with P + H + chemotherapy. PH FDC SC is established as a faster, more convenient, less invasive patient- and health care professional-preferred alternative to P + H IV for HER2-positive BC.