Kong, AnthonyRea, DanielAhmed, SamreenBeck, J ThaddeusLópez López, RafaelBiganzoli, LauraArmstrong, Anne CAglietta, MassimoAlba, EmilioCampone, MarioHsu Schmitz, Shu-FangLefebvre, CarolineAkimov, MikhailLee, Soo-Chin2023-01-252023-01-252016http://hdl.handle.net/10668/10039This 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.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/AUY922HER2HSP90 inhibitorbreast cancertrastuzumabAdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBayes TheoremBreast NeoplasmsCohort StudiesDisease ProgressionDose-Response Relationship, DrugFemaleHSP90 Heat-Shock ProteinsHumansIsoxazolesKaplan-Meier EstimateMiddle AgedNeoplasm MetastasisReceptor, ErbB-2ResorcinolsTrastuzumabTreatment Outcomeresearch article27129177open access10.18632/oncotarget.89741949-2553PMC5122341http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=download&path%5B%5D=8974&path%5B%5D=27169378229100021https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5122341/pdf