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Mini Oral session

3O - Mutation analysis of circulating tumour DNA from baseline and study discontinuation samples in SANDPIPER, a phase III study of taselisib or placebo with fulvestrant in oestrogen receptor-positive, human epidermal growth factor receptor 2-negative, PIK3CA-mutant advanced breast cancer

Date

23 May 2020

Session

Mini Oral session

Presenters

William Jacot

Citation

Annals of Oncology (2020) 31 (suppl_2): S15-S41. 10.1016/annonc/annonc117

Authors

W. Jacot1, H.M. Savage2, S. Dent3, J. Cortés4, Y. Im5, V.C. Dieras6, N. Harbeck7, I.E. Krop8, J. Chen2, E. Sokol9, F. Schimmoller10, J. Hsu10, M. De Laurentiis11, T.R. Wilson2

Author affiliations

  • 1 Medical Oncology, Institut du Cancer de Montpellier (ICM) Val d'Aurelle, 34298 - Montpellier/FR
  • 2 Oncology Biomarker Development, Genentech, Inc., South San Francisco/US
  • 3 Division Of Medical Oncology, The Ottawa Hospital Cancer Centre, Ottawa/CA
  • 4 Breast Cancer And Gynecological Tumors (iob Institute Of Oncology) And Breast Cancer Research Program (vall D’hebron Institute Of Oncology), IOB Institute of Oncology, Quiron Group & Vall d’Hebron Institute of Oncology (VHIO), 08035 - Madrid & Barcelona/ES
  • 5 Division Of Hematology/oncology, Samsung Medical Center, 135-710 - Seoul/KR
  • 6 Clinical Research (institut Curie) And Medical Oncology (centre Eugène Marquis), Institut Curie & Centre Eugène Marquis, Paris/Rennes/FR
  • 7 Gynecology And Obstetrics, Brustzentrum der Universität München (LMU), Munich/DE
  • 8 Breast Oncology, Dana-Farber Cancer Institute, Boston/US
  • 9 Cancer Genomics, Foundation Medicine, Inc., Massachusetts/US
  • 10 Product Development Oncology, Genentech, Inc., South San Francisco/US
  • 11 Experimental Clinical Oncology Of Senology, IRCCS Istituto Nazionale Tumori Fondazione G. Pascale, Naples/IT
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Resources

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Abstract 3O

Background

Activating mutations in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) and AKT1 oncogenes, and mutations in the PTEN tumour suppressor gene, occur in 40–50% of oestrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC). We assessed phosphatidylinositol 3-kinase (PI3K) pathway mutations in circulating tumour DNA (ctDNA) from responding patients in SANDPIPER (NCT02340221), a phase III study of taselisib (PI3K inhibitor) or placebo with fulvestrant in ER-positive, HER2-negative, PIK3CA-mutant locally advanced or metastatic BC.

Methods

Baseline and study discontinuation ctDNA samples were analyzed from 99 patients in SANDPIPER who had baseline tumour PI3KCA mutations (cobas® PIK3CA Mutation Test, Roche Molecular Systems) and had experienced a response or an extended progression-free survival with tumour shrinkage. Samples were assessed by next-generation sequencing (FoundationOne® Liquid assay, Foundation Medicine) using a proprietary analysis pipeline.

Results

85/99 paired samples were evaluable for ctDNA sequencing, with 54 (63.5%) and 85 (100%) PIK3CA mutation-positive by baseline plasma and tissue, respectively. Of the 85 mutations newly detected at study discontinuation (i.e. absent at baseline), the most common were ESR1 (21), TP53 (10), PIK3CA (8), PTEN (8), and ERBB2 (5). Activating AKT1 and loss of function PTEN mutations were identified in the taselisib arm only.

Conclusions

Detection of AKT1 and PTEN mutations in the PI3K pathway within this population suggests possible resistance mechanisms following treatment with PI3K inhibitors. The recent approval of alpelisib in hormone-receptor (HR)-positive, PIK3CA-mutant BC, in addition to the development of novel AKT inhibitors in HR-positive, HER2-negative BC, highlight the importance of understanding changes in the PI3K pathway following treatment with inhibitors.

Clinical trial identification

GO29058/NCT02340221; 24 Jun 2018.

Editorial acknowledgement

Support for third-party writing assistance for this abstract, furnished by Stephen Salem, BSc, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland.

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd.

Funding

F. Hoffmann-La Roche Ltd.

Disclosure

W. Jacot: Advisory/Consultancy, Travel/Accommodation/Expenses, Non-remunerated activity/ies, Support for third-party writing assistance for this abstract: F. Hoffmann-La Roche Ltd; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: Eisai; Advisory/Consultancy, Travel/Accommodation/Expenses: Lilly France; Advisory/Consultancy: MSD; Advisory/Consultancy: Novartis; Travel/Accommodation/Expenses: Chugai Pharma; Travel/Accommodation/Expenses: GlaxoSmithKline; Travel/Accommodation/Expenses: Pierre Fabre; Travel/Accommodation/Expenses: Sanofi Aventis. H.M. Savage: Shareholder/Stockholder/Stock options, Non-remunerated activity/ies, Support for third-party writing assistance for this abstract: F. Hoffmann-La Roche Ltd; Shareholder/Stockholder/Stock options, Full/Part-time employment: Genentech, Inc. S. Dent: Non-remunerated activity/ies, Support for third-party writing assistance for this abstract: F. Hoffmann-La Roche Ltd; Honoraria (self), Research grant/Funding (self): Novartis Canada. J. Cortés: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, Non-remunerated activity/ies, Support for third-party writing assistance for this abstract: F. Hoffmann-La Roche Ltd; Shareholder/Stockholder/Stock options: MedSIR; Honoraria (self), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy: Celgene; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Eisai; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Honoraria (self): Samsung Bioepis; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck Sharp & Dohme; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: Cellestia; Advisory/Consultancy: Biothera Pharmaceuticals; Advisory/Consultancy: Merus; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy, Travel/Accommodation/Expenses: Daiichi Sankyo; Advisory/Consultancy: Erytech; Advisory/Consultancy: Athenex; Advisory/Consultancy: Polyphor; Advisory/Consultancy: Servier; Advisory/Consultancy: GSK; Research grant/Funding (institution): Ariad Pharmaceuticals; Research grant/Funding (institution): Baxalta GmbH/Servier Affaires; Research grant/Funding (institution): Bayer Healthcare; Research grant/Funding (institution): Guardant Health; Research grant/Funding (institution): Piqur Therapeutics; Research grant/Funding (institution): Puma C; Research grant/Funding (institution): Queen Mary University of London; Research grant/Funding (institution): SeaGen. Y-H. Im: Non-remunerated activity/ies, Support for third-party writing assistance for this abstract: F. Hoffmann-La Roche Ltd. V.C. Dieras: Honoraria (self), Advisory/Consultancy, Non-remunerated activity/ies, Support for third-party writing assistance for this abstract: F. Hoffmann-La Roche Ltd; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy: Eli Lilly; Honoraria (self), Advisory/Consultancy: AbbVie; Honoraria (self), Advisory/Consultancy: Seattle Genetics; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Daiichi Sankyo; Honoraria (self), Advisory/Consultancy: Merck Sharp and Dohme. N. Harbeck: Honoraria (self), Non-remunerated activity/ies, support for third-party writing assistance for this abstract: F. Hoffmann-La Roche Ltd; Honoraria (self): Novartis. I.E. Krop: Honoraria (self), Research grant/Funding (institution), Non-remunerated activity/ies, support for third-party writing assistance for this abstract: F. Hoffmann-La Roche Ltd; Honoraria (self), Research grant/Funding (institution): Genentech, Inc.; Research grant/Funding (institution): Pfizer; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Daiichi Sankyo; Honoraria (self): Macrogenics; Honoraria (self): Context Therapeutics; Honoraria (self): Taiho Oncology; Honoraria (self): Celltrion. J. Chen: Shareholder/Stockholder/Stock options, Non-remunerated activity/ies, Support for third-party writing assistance for this abstract: F. Hoffmann-La Roche Ltd; Full/Part-time employment: Genentech, Inc. E. Sokol: Non-remunerated activity/ies, Support for third-party writing assistance for this abstract: F. Hoffmann-La Roche Ltd; Shareholder/Stockholder/Stock options, Full/Part-time employment: Foundation Medicine. F. Schimmoller: Shareholder/Stockholder/Stock options, Non-remunerated activity/ies, Support for third-party writing assistance for this abstract: F. Hoffmann-La Roche Ltd; Full/Part-time employment: Genentech, Inc.; Shareholder/Stockholder/Stock options, Patent or intellectual property interests: Exelixis; Shareholder/Stockholder/Stock options: Teva. J. Hsu: Shareholder/Stockholder/Stock options, Non-remunerated activity/ies, Support for third-party writing assistance for this abstract: F. Hoffmann-La Roche Ltd; Full/Part-time employment: Genentech, Inc. M. De Laurentiis: Honoraria (self), Non-remunerated activity/ies, Support for third-party writing assistance for this abstract: F. Hoffmann-La Roche Ltd; Honoraria (self): Pfizer; Honoraria (self): Novartis; Honoraria (self): Celgene; Honoraria (self): AstraZeneca; Honoraria (self): Eisai; Honoraria (self): Eli Lilly; Honoraria (self): Amgen; Honoraria (self): MSD. T.R. Wilson: Shareholder/Stockholder/Stock options, Non-remunerated activity/ies, Support for third-party writing assistance for this abstract: F. Hoffmann-La Roche Ltd; Full/Part-time employment: Genentech, Inc.

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