Abstract P5-20-09: Pharmacokinetic results of a subcutaneous injection of trastuzumab into the thigh versus into the abdominal wall in patients with HER2-positive primary breast cancer (BC) treated within the neo-/adjuvant GAIN-2 study

Background A new subcutaneous (s.c.) formulation of trastuzumabbecame available in 2013 based on equivalent efficacy, pharmacokinetic (PK) profile and safety with the standard intravenous (i.v.) administration, where the s.c. trastuzumabwas administered only into the thigh. As an s.c. injection into the abdominal wall (abdw) might be more convenient for patients (pts) and health care professionals, the PK profile of s.c. trastuzumabinjected into the thighvs the abdw in pts with HER2+ early BC needs to be evaluated. Methods GAIN-2 study compared two intense dose-dense (idd) anthracycline/ taxanecontaining regimens. After completion of the anthracycline and i.v. trastuzumabgiven concurrently with taxanes, HER2+ BC pts were randomized in a 1:1 ratio to continue adjuvant s.c. trastuzumab600mg fixed dose injected every 3 weeks either into the thighor the abdw. Randomization was stratified according to CT arm [(iddEnPC) vs tailored dd CT (dtEC-dtD)] and age (≤50 vs >50). Pts in the EnPC arm received 14 and in the dtEC-dtD arm 15 cycles of s.c. trastuzumab. For the PK profile of s.c. trastuzumabserum samples collected before cycle 7, on days 2, 4, 8, 15 and 21 of cycle 7 are evaluated. With a total sample size of 30 (15 per group), the simulated 90% two-sided CI for the area under the plasma concentration (AUC 0-last ) will be (0.79-1.27) and for the peak drug concentration (C max ) will be (0.77-1.30). Allowing for a dropout rate of 15%, 18 pts per group will be included in the PK analysis. The primary objective was to assess the PK profile of s.c. trastuzumabinjected into the thighvs the abdw. The secondary objectives included safety and tolerability. Results The per-protocol (pp) set consists of 30 pts (17 in the thighgroup and 13 in the abdw group). Baseline characteristics were well balanced between the groups. The log-transformed Geometric Least Square Means (GLSM) for C max were 11.77 and 11.52 in the thighand the abdw group, respectively. The geo-mean ratio (on the original scale) for C max was 1.29 (90% CI 1.05-1.58). The log-transformed GLSM for AUC 0-last were 14.54 and 14.28 in the thighand the abdw group, respectively. The geo-mean ratio for AUC 0-last was 1.29 (90% CI 1.02-1.63). Overall 29 pts (96.7%) reported any grade and 5 pts (16.7%) high grade adverse events (AEs). The incidence of any grade AEs was similar between the two groups. The most common AEs were anemia (70.6% for the thighvs 61.5% for the abdw group, p=0.705), leukopenia (80.0% for both groups, p=1.000) and fatigue (47.1% for the thighvs 76.9% for the abdw group, p=0.141). 6 serious AEs were reported (2 in the thighvs 4 in the abdw group). The final PK results of s.c. trastuzumabwill be presented at the meeting. Conclusions Bioavailability of s.c. trastuzumabas reflected by peak and total exposure measured in cycle 7 was approx. 30% higher if administered into the thighthan into the abdw in pts with HER2+ primary BC treated after dose-dense CT plus i.v. trastuzumab. However, no increased toxicity was observed. Study limitations were that no cross-over design was used and number of pts satisfying criteria for pp-set were different in the arms. Citation Format: Mobus V, Mahlberg R, Janni W, Tome O, Marme F, Forstbauer H, Reimer T, von der Assen A, Reinisch M, Lorenz R, Schmatloch S, Schmidt M, Sinn B, Klutinus N, Stickeler E, Untch M, Seiler S, Burchardi N, von Minckwitz G, Loibl S. Pharmacokinetic results of a subcutaneous injection of trastuzumabinto the thighversus into the abdominal wall in patients with HER2-positive primary breast cancer (BC) treated within the neo-/adjuvant GAIN-2 study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-20-09.