Research Papers:
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
Metrics: PDF 1903 views | HTML 2384 views | ?
Abstract
Anthony Kong1,2, Daniel Rea2, Samreen Ahmed3, J. Thaddeus Beck4, Rafael López López5, Laura Biganzoli6, Anne C. Armstrong7, Massimo Aglietta8, Emilio Alba9, Mario Campone10, Shu-Fang Hsu Schmitz11, Caroline Lefebvre12, Mikhail Akimov13, Soo-Chin Lee14
1Previous address: Churchill Hospital, Oxford University Hospitals NHS Trust and University of Oxford, Oxford, United Kingdom
2School of Cancer Sciences, University of Birmingham, Birmingham, United Kingdom
3Department of Oncology, University Hospitals of Leicester, Leicester Royal Infirmary, Leicester, United Kingdom
4Department of Oncology, Highlands Oncology Group, Fayetteville, Arkansas, USA
5Department of Oncology, Hospital Clinico Universitario, Santiago de Compostela, Spain
6Department of Medical Oncology, Nuovo Ospedale di Prato, Prato, Italy
7Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom
8Department of Medical Oncology, University of Torino, FPO-IRCCS, Candiolo, Italy
9Department of Medical Oncology, University Hospital, IBIMA, Malaga, Spain
10Department of Medical Oncology, Institut de Cancérologie de l'ouest René Gauducheau, Nantes, France
11Early Clinical Biostatistics, Oncology, Novartis Pharma AG, Basel, Switzerland
12Translational Clinical Oncology, Novartis Pharma AG, Basel, Switzerland
13Oncology Global Development, Novartis Pharma AG, Basel, Switzerland
14Department of Hematology-Oncology, National University Cancer Institute Singapore, Singapore
Correspondence to:
Anthony Kong, e-mail: [email protected]
Keywords: breast cancer, HER2, HSP90 inhibitor, AUY922, trastuzumab
Received: January 28, 2016 Accepted: March 31, 2016 Published: April 25, 2016
ABSTRACT
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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 8974