2026-04-29T19:34:52Zhttps://repisalud.isciii.es/rest/oai/request
oai:repisalud.isciii.es:20.500.12105/171162024-09-21T19:10:23Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927
Repisalud author Kong, Anthony author Rea, Daniel author Ahmed, Samreen author Beck, J Thaddeus author López López, Rafael author Biganzoli, Laura author Armstrong, Anne C author Aglietta, Massimo author Alba, Emilio author Campone, Mario author Hsu Schmitz, Shu-Fang author Lefebvre, Caroline author Akimov, Mikhail author Lee, Soo-Chin authoraffiliation [Kong, Anthony] Oxford Univ Hosp NHS Trust, Churchill Hosp, Oxford, England authoraffiliation [Kong, Anthony] Univ Oxford, Oxford, England authoraffiliation [Kong, Anthony] Univ Birmingham, Sch Canc Sci, Birmingham, W Midlands, England authoraffiliation [Rea, Daniel] Univ Birmingham, Sch Canc Sci, Birmingham, W Midlands, England authoraffiliation [Ahmed, Samreen] Leicester Royal Infirm, Univ Hosp Leicester, Dept Oncol, Leicester, Leics, England authoraffiliation [Beck, J. Thaddeus] Highlands Oncol Grp, Dept Oncol, Fayetteville, AR USA authoraffiliation [Lopez, Rafael Lopez] Hosp Clin Univ, Dept Oncol, Santiago De Compostela, Spain authoraffiliation [Biganzoli, Laura] Nuovo Osped Prato, Dept Med Oncol, Prato, Italy authoraffiliation [Armstrong, Anne C.] Christie NHS Fdn Trust, Dept Med Oncol, Manchester, Lancs, England authoraffiliation [Aglietta, Massimo] Univ Turin, Dept Med Oncol, FPO IRCCS, Candiolo, Italy authoraffiliation [Alba, Emilio] IBIMA, Univ Hosp, Dept Med Oncol, Malaga, Spain authoraffiliation [Campone, Mario] Inst Canc Ouest Rene Gauducheau, Dept Med Oncol, Nantes, France authoraffiliation [Schmitz, Shu-Fang Hsu] Novartis Pharma AG, Early Clin Biostat, Oncol, Basel, Switzerland authoraffiliation [Akimov, Mikhail] Novartis Pharma AG, Oncol Global Dev, Basel, Switzerland authoraffiliation [Lee, Soo-Chin] Natl Univ Singapore, Canc Inst Singapore, Dept Hematol Oncol, Singapore 117548, Singapore 2024-01-16T12:15:51Z 2024-01-16T12:15:51Z 2016 10.18632/oncotarget.8974 1949-2553 Oncotarget http://hdl.handle.net/10668/10039 27129177 http://hdl.handle.net/20.500.12105/17116 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. eng AUY922 HER2 HSP90 inhibitor breast cancer trastuzumab 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. research article