Abstract 114P
Background
The primary analysis of the FeDeriCa study (NCT03493854; Tan AR, et al. Lancet Oncol 2021) showed that PH FDC SC cycle 7 P and H serum trough concentrations were non-inferior to intravenous (IV) P and H, with comparable total pathological complete response rates and safety profiles when given as neoadjuvant therapy for HER2-positive EBC. Here we report long-term efficacy and safety data.
Methods
Patients (pts) had HER2-positive operable, locally advanced or inflammatory stage II–IIIC BC and left ventricular ejection fraction ≥55%. They received eight cycles of neoadjuvant chemotherapy (one of two standard regimens chosen by the investigator) + P IV (840 mg loading dose then 420 mg maintenance) + H IV (8 mg/kg then 6 mg/kg) or PH FDC SC (1200 mg P/600 mg H then 600 mg each as FDC SC) every 3 weeks during cycles 5–8 in a 1:1 randomisation design. Pts continued adjuvant HER2-targeted treatment after surgery, per randomisation, to complete 18 cycles. Secondary endpoints included invasive disease-free survival (iDFS), event-free survival (EFS), distant recurrence-free interval (DRFI), overall survival (OS) and safety (focusing on cardiac adverse events).
Results
Data cut-off was 2 Jun, 2023; median follow-up was 51.4 months in the P + H IV arm and 51.2 months in the PH FDC SC arm. Long-term efficacy data are shown in the table. No new safety signals, including for cardiac safety, were observed. Table: 114P
| P + H IV n = 252 | PH FDC SC n = 248 | ||
| iDFS | Pts who underwent surgery, n | 239 | 234 |
| Pts with event, n (%) | 23 (9.6) | 26 (11.1) | |
| Unstratified hazard ratio (HR)(95% confidence interval [CI]) | 1.13 (0.64, 1.97) | ||
| 4-year event-free rate (95% CI) | 89.5 (85.4, 93.6) | 88.5 (84.3, 92.7) | |
| EFS | Pts, n | 252 | 248 |
| Pts with event, n (%) | 29 (11.5) | 32 (12.9) | |
| HR (95% CI) | 1.20 (0.72, 1.98) | ||
| 4-year event-free rate (95% CI) | 88.5 (84.4, 92.5) | 86.6 (82.2, 90.9) | |
| DRFI | Pts, n | 252 | 248 |
| Pts with event, n (%) | 18 (7.1) | 19 (7.7) | |
| HR (95% CI) | 1.17 (0.61, 2.24) | ||
| 4-year event-free rate (95% CI) | 92.5 (89.2, 95.8) | 91.9 (88.4, 95.4) | |
| OS | Pts, n | 252 | 248 |
| Pts with event, n % | 12 (4.8) | 14 (5.6) | |
| HR (95% CI) | 1.26 (0.58, 2.72) | ||
| 4-year event-free rate (95% CI) | 95.5 (92.9, 98.1) | 94.1 (91.1, 97.1) |
Conclusions
The long-term efficacy of PH FDC SC was comparable to that of P + H IV. Safety remained similar to P + H IV and consistent with P + H + chemotherapy. Overall, these findings support the primary analysis results. PH FDC SC is established as a faster, more convenient, less invasive, pt- and healthcare professional-preferred alternative to P + H IV for pts with HER2-positive BC.
Clinical trial identification
NCT03493854.
Editorial acknowledgement
Support for third-party writing assistance for this abstract, furnished by Chantel Swart, PhD, of Nucleus Global, an Inizio company.
Legal entity responsible for the study
F. Hoffmann-La Roche Ltd.
Funding
F. Hoffmann-La Roche Ltd.
Disclosure
C. Jackisch: Financial Interests, Personal, Invited Speaker: Roche, Exact Sciences, Gilead, Molecular Health; Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis, Daiichi Sankyo, Pfizer. S. Im: Financial Interests, Personal, Advisory Board, no payment: AstraZeneca, Novartis, Eisai, Roche, Hanmi, Pfizer, Lilly, MSD, GSK, Daiichi Sankyo; Financial Interests, Institutional, Advisory Board: Bertis; Financial Interests, Personal, Advisory Board: Idience; Financial Interests, Institutional, Research Grant: AstraZeneca, Pfizer, Roche, Eisai, Dae Woong; Financial Interests, Institutional, Invited Speaker, Clinical Trial Budget: AstraZeneca, Eisai, Hanmi, Novartis, Roche, Pfizer, Daiichi Sankyo, MSD, Lilly; Financial Interests, Institutional, Research Grant, Clinical Trial Budget: Boryung Pharm. A. Mattar: Financial Interests, Personal, Advisory Board: Roche, Novartis, Pierre Fabre, AstraZeneca, Exact Sciences; Financial Interests, Personal, Advisory Role: Roche, Novartis, Pierre Fabre, AstraZeneca, Exact Sciences; Non-Financial Interests, Personal, Other, Research funding in the form of third-party writing assistance from F. Hoffmann-La Roche Ltd: F. Hoffmann-La Roche Ltd. R. Colomer Bosch: Non-Financial Interests, Personal, Other, Research funding in the form of third-party writing assistance from F. Hoffmann-La Roche Ltd: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Other, Honoraria: Roche, Eli Lilly, MSD, AstraZeneca. D. Stroyakovskiy: Financial Interests, Personal, Speaker’s Bureau: Roche/Genentech, Bristol Meyers Squibb, BioCad, AstraZeneca; Non-Financial Interests, Personal, Other, Research funding in the form of third-party writing assistance from F. Hoffmann-La Roche Ltd: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Other, Travel, accommodation, expenses: AstraZeneca, Novartis, Roche. Z. Nowecki: Non-Financial Interests, Personal, Other, Research funding in the form of third-party writing assistance from F. Hoffmann-La Roche Ltd: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Other, Travel, accommodation, expenses: Roche. M. De Laurentiis: Financial Interests, Personal, Advisory Board: Pfizer, Novartis, Roche, Celgene, AstraZeneca, Eisai, Lilly, Amgen, MSD, Pierre Fabre, Genomic Health, Daiichi Sankyo, Veracyte, Gilead; Financial Interests, Personal, Advisory Role: Pfizer, Novartis, Roche, Celgene, AstraZeneca, Eisai, Lilly, Amgen, MSD, Pierre Fabre, Genomic Health, Daiichi Sankyo; Non-Financial Interests, Personal, Other, Research funding in the form of third-party writing assistance from F. Hoffmann-La Roche Ltd: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Other, Speaker's honoraria: Pfizer, Novartis, Roche, Celgene, AstraZeneca, Eisai, Lilly, Amgen, MSD, Pierre Fabre, Genomic Health, Daiichi Sankyo, Veracyte, Gilead. J. Pierga: Financial Interests, Personal, Advisory Board: Pfizer, Lilly, Seagen, MSD, Novartis, Exact Sciences, Gilead, AstraZeneca, Eisai; Financial Interests, Personal, Invited Speaker: Roche, Daiichi Sankyo, Menarini, Veracyte, Pfizer, Lilly, Seagen, MSD, Novartis, Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Novartis, Daiichi Sankyo; Financial Interests, Institutional, Other, IDMC: Sanofi; Financial Interests, Institutional, Funding: Servier. K.H. Jung: Financial Interests, Personal, Advisory Board: Roche, Novartis, Daiichi Sankyo, MSD, Pfizer, Gilead, Eisai, AstraZeneca, Takeda, Celgene; Non-Financial Interests, Personal, Other, Research funding in the form of third-party writing assistance from F. Hoffmann-La Roche Ltd: F. Hoffmann-La Roche Ltd. C. Schem: Financial Interests, Personal, Advisory Board: Roche, Novartis, Lilly, AstraZeneca, Daiichi Sankyo Sanyo; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Roche, Gilead. S.H. Heeson, V. Craine, B. Wang, E. Restuccia: Financial Interests, Personal, Full or part-time Employment: Genentech, Inc.; Financial Interests, Personal, Ownership Interest: F. Hoffmann-La Roche Ltd.; Non-Financial Interests, Personal, Other, Research funding in the form of third-party writing assistance from F. Hoffmann-La Roche Ltd: F. Hoffmann-La Roche Ltd. A.R. Tan: Financial Interests, Personal, Advisory Board: Jazz Pharmaceuticals, Stemline Therapeutics, AstraZeneca; Financial Interests, Institutional, Invited Speaker: Genentech/Roche, Merck, Arvinas; Non-Financial Interests, Leadership Role: ASCO Tapur Publications Committee.