The Phase III, non-randomised, multinational, open-label SafeHer study (NCT01566721) confirmed the safety and tolerability profile of 600 mg fixed-dose subcutaneous trastuzumab (Herceptin® SC [H SC]), administered every 3 weeks (q3w) for 18 cycles/1 year from an H SC Vial via hand-held syringe or from a single-use injection device (SID), as adjuvant therapy for HER2-positive early breast cancer (Gligorov J, et al. EBCC 2016; P326). The safety and tolerability of H SC 600 mg fixed-dose therapy may be affected by patients' body weights and active medical conditions, especially in patients with lower body weights. We assessed these factors in an exploratory analysis of SafeHer.
Adverse events (AEs) and serious AEs (SAEs) were recorded/graded per National Cancer Institute – Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4.0. Congestive heart failure (CHF) was assessed by NCI-CTCAE v4.0/New York Heart Association functional classification. Results are descriptive. Data are from the combined H SC Vial and H SC SID cohorts, from the first H SC dose until 28 days after the last dose (plus a 5-day window). SafeHer study follow-up will continue for 5 years.
Safety and active medical conditions of interest by weight subgroup are shown in the table.
|Patients, n (%)||Overall N = 2573||Very- low weight 59– ≤ 67 kg n = 641||Quartile 3 >67– ≤ 77 kg n = 625||Quartile 4 >77 kg n = 623|
|Any grade AE||2282 (89)1||36 (90)||258 (88)||590 (87)||566 (88)||558 (89)||561 (90)|
|Grade ≥3 AE||596 (23)1||8 (20)||54 (18)||121 (18)||152 (24)||155 (25)||167 (27)|
|Cardiac disorder||24 (1)1||0||3 (1)||6 (1)||5 (1)||7 (1)||6 (1)|
In this SafeHer subgroup analysis, the safety results were comparable for the H SC 600 mg q3w fixed dose among the lower-body-weight subgroups and the overall patient population. In the higher-body-weight subgroup, grade ≥3 AE and SAE rates were slightly higher than the overall patient population, which may be influenced by the higher rate of active medical conditions in the higher-body-weight subgroups; nevertheless, grade ≥3 and serious cardiac disorders remained comparable across all weight subgroups.
Clinical trial identification
Legal entity responsible for the study
F. Hoffmann-La Roche Ltd.
F. Hoffmann-La Roche Ltd.
B. Ataseven: Membership of an advisory board (Roche). Other substantive relationships (honorarium for lectures: Roche, AstraZeneca; Travel expenses support: Roche). M. Verrill: Stock ownership (Roche, Bayer); Membership of an advisory board (Roche, Celgene, AstraZeneca, Novartis, Pfizer, Teva, Chugai); Corporate-sponsored research (Roche, Novartis, Amgen). X. Pivot: Consultant with honorarium for Roche, Amgen, Novartis, Eisai, Pierre Fabre. M. De Laurentiis: Membership of an advisory board (Roche, Novartis, Celgene, Pfizer, Eisai). N. Al-Sakaff: Stock ownership (Roche). Employee of Roche.
S. Lauer: Other substantive relationships (contract work for F. Hoffmann-La Roche). M. Shing: Other substantive relationships (Employee of Genentech, Inc.). J. Gligorov: Consultancy: Roche-Genentech; Eisai Honoraria: Teva; Novartis-GSK; GenomicHealth. H.A. Azim: Membership of an advisory board (Roche, Pfizer, Novartis & Amgen); Corporate-sponsored research (Bayer & Pfizer). All other authors have declared no conflicts of interest.