Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/19971
Title: A phase 1b dose-escalation and expansion study of the BCL-2 inhibitor venetoclax combined with tamoxifen in ER and BCL-2-positive metastatic breast cancer.
Austin Authors: Lindeman, Geoffrey J;Lok, Sheau Wen;Whittle, James R;Vaillant, Francois;Teh, Charis E;Lo, Louisa L;Policheni, Antonia N;Bergin, Alice R T;Desai, Jayesh;Ftouni, Sarah;Gandolfo, Luke C;Liew, Danny;Liu, He K;Mann, G Bruce;Moodie, Kate;Murugasu, Anand;Pal, Bhupinder;Roberts, Andrew W;Rosenthal, Mark A;Shackleton, Kylie;Silva, Maria J;Siow, Zhen R;Smyth, Gordon K;Taylor, Leanne;Travers, Avraham;Yeo, Belinda ;Yeung, Miriam M;Zivanovic Bujak, Andjelija;Dawson, Sarah-Jane;Gray, Daniel H D;Visvader, Jane E
Affiliation: Stem Cells and Cancer Division, Walter and Eliza Hall Institute of Medical Research lindeman@wehi.edu.au
Stem Cells and Cancer Division, Walter and Eliza Hall Institute of Medical Research
VBCRC Laboratory, The Walter and Eliza Hall Institute of Medical Research
Molecular Genetics of Cancer, The Walter and Eliza Hall Institute of Medical Research
Medical Oncology, Peter MacCallum Cancer Centre
The Walter and Eliza Hall Institute of Medical Research
Peter MacCallum Cancer Centre
Department of Medical Oncology, Peter MacCallum Cancer Centre..
Cancer Genomics and Genetics Program, Peter MacCallum Cancer Centre
Walter and Eliza Hall Institute of Medical Research
Monash University
Walter and Eliza Hall Institute of Medical Research
Department of Surgery, Royal Melbourne Hospital, University of Melbourne
Cancer Imaging, Peter MacCallum Cancer Centre
Anatomical Pathology, Royal Melbourne Hospital
Walter and Eliza Hall Institute of Medical Research..
Cancer and Haematology, Walter and Eliza Hall Institute..
Peter MacCallum Cancer Centre
Familial cancer Centre, Royal Melbourne Hospital
Peter MacCallum Cancer Centre
Royal Melbourne Hospital
Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research
Melbourne Health Tissue Bank, Royal Melbourne Hospital..
Medical Oncology, Royal Melbourne Hospital..
Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
Research, Peter MacCallum Cancer Centre
Cancer Research, Peter McCallum Cancer Centre
Molecular Genetics of Cancer, The Walter and Eliza Hall Institute of Medical Research
Stem Cells and Cancer Division, The Walter and Eliza Hall Institute
Issue Date: 5-Dec-2018
metadata.dc.date: 2018-12-05
Publication information: Cancer discovery 2018; online first: 5 December
Abstract: Venetoclax, a potent and selective BCL-2 inhibitor, synergizes with endocrine therapy in pre-clinical models of ER-positive breast cancer. Using a phase 1b 3+3 dose escalation and expansion study design, 33 patients with ER and BCL-2-positive metastatic disease (mean prior regimens, 2; range 0-8) were treated with daily tamoxifen (20 mg) and venetoclax (200-800 mg). Apart from uncomplicated 'on-target' lymphopenia, no dose-limiting toxicities or high-grade adverse events were observed in the escalation phase (15 patients), and 800 mg was selected as the recommended phase 2 dose (RP2D). In the expansion phase (18 patients), few high-grade treatment-related adverse events were observed. For 24 patients treated at the RP2D, the confirmed radiologic response rate was 54% and clinical benefit rate 75%. Treatment responses were pre-empted by metabolic responses (FDG-PET) at 4 weeks and correlated with serial changes in circulating tumor DNA. Radiologic responses (40%) and clinical benefit (70%) were observed in 10 patients with plasma-detected ESR1 mutations.
URI: http://ahro.austin.org.au/austinjspui/handle/1/19971
DOI: 10.1158/2159-8290.CD-18-1151
ORCID: 0000-0001-9386-2416
0000-0003-3229-3760
0000-0001-7426-7953
0000-0002-2150-879X
0000-0002-7341-5720
0000-0001-9221-2892
0000-0002-9455-1887
0000-0002-9218-9917
PubMed URL: 30518523
Type: Journal Article
Appears in Collections:Journal articles

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