PH FDC SC was shown to be non-inferior to intravenous (IV) P and H in cycle 7 serum trough concentrations (Ctrough), with comparable total pathological complete response (tpCR) rates and safety profiles, in pts with HER2-positive EBC (FeDeriCa; NCT03493854). It is also less invasive, preferred by pts and reduces pt chair time. FDChina (NCT04024462) assesses (neo)adjuvant PH FDC SC in Chinese pts.
Pts with operable or locally advanced/inflammatory disease (stage II–IIIC; primary tumour >2cm/node-positive) were randomised 1:1 to four doxorubicin (60 mg/m2) + cyclophosphamide (600 mg/m2) cycles every 3 weeks (q3w), then four docetaxel (D; 75–100 mg/m2) cycles q3w. Pts received PH FDC SC (loading: 1200 mg P + 600 mg H; maintenance: 600 mg P + 600 mg H) or PH IV (loading: 840 mg/8 mg/kg; maintenance: 420 mg/6 mg/kg) q3w alongside D. Pts then had surgery before continuing anti-HER2 therapy for 14 cycles. Co-primary endpoints: cycle 7 P and H Ctrough. Secondary endpoints: tpCR, long-term efficacy, safety. Stratification factors: hormone receptor status, stage at presentation.
Intention-to-treat population: 99 pts (PH FDC SC) vs 101 (PH IV). Safety and per protocol pharmacokinetic populations had 100 and 89 pts per arm. Baseline characteristics were balanced between arms. P and H cycle 7 geometric mean ratios (Ctrough SC/IV) were 1.07 (90% confidence interval [CI]: 0.99–1.15) and 1.55 (1.44–1.67), with the lower limit exceeding the prespecified non-inferiority margin (0.8). tpCR rates were 55.6% (95% CI: 45.2–65.6) vs 56.4% (46.2–66.3) in the PH FDC SC vs PH IV arms, respectively. Grade ≥3 AEs occurred in 72% vs 69% of pts; injection/administration-related reactions within 24 hrs in 14% vs 12%; serious AEs in 18% vs 19%; fatal AEs in 1% (cardiac) vs 0. Incidence of anaphylaxis/hypersensitivity was 4% vs 1% and diarrhoea 27% vs 39% (both were mostly low grade).
FDChina met its co-primary endpoints: PH FDC SC P and H cycle 7 Ctrough were non-inferior to those for PH IV. tpCR rates were comparable between arms. No new safety signals were identified. This suggests PH FDC SC may be a viable treatment option for Chinese pts.
NCT04024462.
Research support in the form of third-party writing assistance for this abstract, furnished by Katie Wilson, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd., Basel, Switzerland.
F. Hoffmann-La Roche Ltd.
F. Hoffmann-La Roche Ltd.
Z. Shao, T. Huang, Z. Fan, Y. Wang, X. Yan, H. Yang, S. Wang, D. Pang, H. Li, H. Wang, C. Geng, L. Huang: Financial Interests, Institutional, Funding, Research funding, Investigator fees for this study: F. Hoffmann-La Roche Ltd.; Non-Financial Interests, Personal, Funding, Research funding, Support for third-party writing assistance: F. Hoffmann-La Roche Ltd. A. Siddiqui: Financial Interests, Personal, Full or part-time Employment: Roche Products Limited; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd.; Non-Financial Interests, Personal, Funding, Research funding, Support for third-party writing assistance: F. Hoffmann-La Roche Ltd. B. Wang: Financial Interests, Personal, Full or part-time Employment: Genentech, Inc.; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd.; Non-Financial Interests, Personal, Funding, Research funding, Support for third-party writing assistance: F. Hoffmann-La Roche Ltd. B. Xie: Financial Interests, Personal, Full or part-time Employment, Prior full-time employment; left Roche on 22 June 2022: Roche (China) Holding Co. Ltd.; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd.; Non-Financial Interests, Personal, Funding, Research funding, Support for third-party writing assistance: F. Hoffmann-La Roche Ltd. G. Sun: Financial Interests, Personal, Full or part-time Employment: Roche (China) Holding Co. Ltd.; Financial Interests, Personal, Stocks/Shares, Owns stocks in Roche: F. Hoffmann-La Roche Ltd.; Non-Financial Interests, Personal, Funding, Research funding, Support for third-party writing assistance: F. Hoffmann-La Roche Ltd. E. Restuccia: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd.; Non-Financial Interests, Personal, Funding, Research funding, Support for third-party writing assistance: F. Hoffmann-La Roche Ltd.