Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/23314
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dc.contributor.authorLok, Sheau W-
dc.contributor.authorWhittle, James R-
dc.contributor.authorVaillant, François-
dc.contributor.authorTeh, Charis E-
dc.contributor.authorLo, Louisa L-
dc.contributor.authorPolicheni, Antonia N-
dc.contributor.authorBergin, Alice R T-
dc.contributor.authorDesai, Jayesh-
dc.contributor.authorFtouni, Sarah-
dc.contributor.authorGandolfo, Luke C-
dc.contributor.authorLiew, Danny-
dc.contributor.authorLiu, He K-
dc.contributor.authorMann, G Bruce-
dc.contributor.authorMoodie, Kate-
dc.contributor.authorMurugasu, Anand-
dc.contributor.authorPal, Bhupinder-
dc.contributor.authorRoberts, Andrew W-
dc.contributor.authorRosenthal, Mark A-
dc.contributor.authorShackleton, Kylie-
dc.contributor.authorSilva, Maria João-
dc.contributor.authorSiow, Zhen R-
dc.contributor.authorSmyth, Gordon K-
dc.contributor.authorTaylor, Leanne-
dc.contributor.authorTravers, Avraham-
dc.contributor.authorYeo, Belinda-
dc.contributor.authorYeung, Miriam M-
dc.contributor.authorBujak, Andjelija Zivanovic-
dc.contributor.authorDawson, Sarah-Jane-
dc.contributor.authorGray, Daniel H D-
dc.contributor.authorVisvader, Jane E-
dc.contributor.authorLindeman, Geoffrey J-
dc.date2018-12-05-
dc.date.accessioned2020-05-25T05:23:37Z-
dc.date.available2020-05-25T05:23:37Z-
dc.date.issued2019-03-
dc.identifier.citationCancer discovery 2019; 9(3): 354-369-
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/23314-
dc.description.abstractVenetoclax, a potent and selective BCL2 inhibitor, synergizes with endocrine therapy in preclinical models of ER-positive breast cancer. Using a phase Ib 3 + 3 dose-escalation and expansion study design, 33 patients with ER and BCL2-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 II 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 the clinical benefit rate was 75%. Treatment responses were preempted 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. SIGNIFICANCE: In the first clinical study to evaluate venetoclax in a solid tumor, we demonstrate that combining venetoclax with endocrine therapy has a tolerable safety profile and elicits notable activity in ER and BCL2-positive metastatic breast cancer. These findings support further investigation of combination therapy for patients with BCL2-positive tumors.See related commentary by Drago et al., p. 323.This article is highlighted in the In This Issue feature, p. 305.-
dc.language.isoeng-
dc.titleA Phase Ib Dose-Escalation and Expansion Study of the BCL2 Inhibitor Venetoclax Combined with Tamoxifen in ER and BCL2-Positive Metastatic Breast Cancer.-
dc.typeJournal Article-
dc.identifier.journaltitleCancer discovery-
dc.identifier.affiliationAustin Health, Heidelberg, Victoria, Australiaen
dc.identifier.affiliationThe Peter MacCallum Cancer Centre, Melbourne, Victoria, Australiaen
dc.identifier.affiliationThe Royal Melbourne Hospital, Melbourne, Victoria, Australiaen
dc.identifier.affiliationThe Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australiaen
dc.identifier.affiliationThe University of Melbourne, Melbourne, Victoria, Australiaen
dc.identifier.affiliationSchool of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australiaen
dc.identifier.affiliationThe Royal Women's Hospital, Melbourne, Victoria, Australiaen
dc.identifier.affiliationOlivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australiaen
dc.identifier.doi10.1158/2159-8290.CD-18-1151-
dc.identifier.orcid0000-0003-3229-3760-
dc.identifier.orcid0000-0002-3684-4331en
dc.identifier.orcid0000-0001-9386-2416en
dc.identifier.orcid0000-0002-9218-9917en
dc.identifier.orcid0000-0001-7426-7953-
dc.identifier.orcid0000-0002-2150-879X-
dc.identifier.orcid0000-0002-7341-5720-
dc.identifier.orcid0000-0001-9221-2892-
dc.identifier.orcid0000-0002-9455-1887-
dc.identifier.pubmedid30518523-
dc.type.austinClinical Trial, Phase I-
dc.type.austinJournal Article-
dc.type.austinMulticenter Study-
dc.type.austinResearch Support, Non-U.S. Gov't-
local.name.researcherYeo, Belinda
item.languageiso639-1en-
item.fulltextNo Fulltext-
item.grantfulltextnone-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
item.openairetypeJournal Article-
crisitem.author.deptOlivia Newton-John Cancer Research Institute-
crisitem.author.deptMedical Oncology-
crisitem.author.deptOlivia Newton-John Cancer Wellness and Research Centre-
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