RT Journal Article
T1 Phase 1B/2 study of the HSP90 inhibitor AUY922 plus trastuzumab in metastatic HER2-positive breast cancer patients who have progressed on trastuzumab-based regimen.
A1 Kong, Anthony
A1 Rea, Daniel
A1 Ahmed, Samreen
A1 Beck, J Thaddeus
A1 López López, Rafael
A1 Biganzoli, Laura
A1 Armstrong, Anne C
A1 Aglietta, Massimo
A1 Alba, Emilio
A1 Campone, Mario
A1 Hsu Schmitz, Shu-Fang
A1 Lefebvre, Caroline
A1 Akimov, Mikhail
A1 Lee, Soo-Chin
K1 AUY922
K1 HER2
K1 HSP90 inhibitor
K1 breast cancer
K1 trastuzumab
AB This open-label, multicenter, phase 1B/2 trial assessed AUY922 plus trastuzumab in patients with locally advanced or metastatic HER2-positive breast cancer previously treated with chemotherapy and anti-HER2 therapy. This study was composed of a dose-escalation part with AUY922 administered weekly at escalating doses with trastuzumab 2 mg/kg/week (phase 1B), followed by a phase 2 part using the same regimen at recommended phase 2 dose (RP2D). The primary objectives were to determine the maximum tolerated dose (MTD) and/or RP2D (phase 1B), and to evaluate preliminary antitumor activity (phase 2) of AUY922 plus trastuzumab at MTD/RP2D. Forty-five patients were treated with AUY922 plus trastuzumab (4 in phase 1B with AUY922 at 55 mg/m2 and 41 in phase 1B/2 with AUY922 at 70 mg/m2 [7 in phase 1B and 34 in phase 2]). One patient in phase 1B (70 mg/m2) experienced a dose-limiting toxicity (grade 3 diarrhea); the RP2D was weekly AUY922 70 mg/m2 plus trastuzumab. Of the 41 patients in the 70 mg/m2 cohort, the overall response rate (complete or partial responses) was 22.0% and 48.8% patients had stable disease. Study treatment-related adverse events occurred in 97.8% of patients; of these, 31.1% were grade 3 or 4. Forty-one patients (91.1%) reported ocular events (82.3% had grade 1 or 2 events). Two patients (4.4%) had ocular events leading to the permanent discontinuation of study treatment. AUY922 at 70 mg/m2 plus trastuzumab standard therapy is well tolerated and active in patients with HER2-positive metastatic breast cancer who progressed on trastuzumab-based therapy.
YR 2016
FD 2016
LK http://hdl.handle.net/10668/10039
UL http://hdl.handle.net/10668/10039
LA en
DS RISalud
RD Apr 12, 2025