To explore safety and tolerability of 600 mg fixed-dose subcutaneous (SC) trastuzumab (Herceptin® SC [H SC]), administered every 3 weeks (q3w) for 18 cycles via hand-held syringe, as adjuvant therapy for HER2-positive early breast cancer (EBC) in patients (pts) with lower body weight and in Asian pts in Cohort A of the SafeHer study. Pts in Cohort B receive H SC via single-use injection device and treatment was ongoing at the time of clinical cutoff.
Adverse events (AEs) and serious AEs (SAEs) were recorded/graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) 4.0; congestive heart failure (CHF), according to NCI-CTCAE 4.0/New York Heart Association functional classification. Lower-weight subgroups were pts weighing <45 kg, ≤53 kg (lowest weight decile) and ≤59 kg (lowest weight quartile). Results are from a planned interim analysis; follow-up will continue for 5 years.
SafeHer interim results are from the first dose until 4 weeks after the last H SC dose (13 months' follow-up for pts who received 18 H SC cycles). Cohort A's safety population comprises 1864 pts; 1563 (84%) received 18 H SC cycles and 295 (16%) are Asian. Among the 31 pts weighing <45 kg, the 226 pts weighing ≤53 kg and the 501 pts weighing ≤59 kg, there was a greater proportion of Asian pts compared with the overall population (55%, 43% and 34%, respectively, compared with 16%). Overall safety, safety in lower-weight groups and safety in Asian pts are shown in the table.
|Pts, n (%)||Cohort A overall n = 1864||<45 kg n = 31||Lowest weight decile: ≤53 kg n = 226||Lowest weight quartile: ≤59 kg n = 501||Asian pts n = 295|
|Any grade AE||1628 (87)||27 (87)||197 (87)||428 (85)||254 (86)|
|≥grade 3 AE||432 (23)||8 (26)||40 (18)||89 (18)||48 (16)|
|SAE||235 (13)||3 (10)||25 (11)||51 (10)||33 (11)|
|Cardiac AE||310 (17)||5 (16)||24 (11)||58 (12)||38 (13)|
|CHF||10 (1)||0||2 (1)||4 (1)||4 (1)|
In this SafeHer Phase III study subgroup analysis, the safety results were similar for the H SC 600 mg q3w fixed dose among lower-weight and Asian pts, relative to the overall population. Thus, safety and tolerability of the H SC 600 mg q3w fixed dose is confirmed as adjuvant therapy for these important HER2-positive EBC pt populations.
Clinical trial identification
M. Shing: Other Substantive Relationships - Genentech employee. K.H. Jung: Corporate-sponsored Research - Eisai Korea. B. Ataseven, H.A. Azim, J. Gligorov: Advisory Board - Roche; Corporate-sponsored Research – Roche. M. Verrill: Advisory Board ‐ Fees from Roche; Corporate‐sponsored Research ‐ Institutional funding from Roche; Other Substanstve Relationships ‐ Fees from speaking for Roche. M. De Laurentiis: Advisory Board - Novartis, Roche, Celgene, AstraZeneca, Genomic Health. N. Al-Sakaff: Ownership - Roche shares; Other Substantive Relationships - Roche employee. S. Lauer: Other Substantive Relationships - Roche contractor. All other authors have declared no conflicts of interest.