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Comprehensive genomic profiling (CGP) of carcinoma of unknown primary origin (CUP): Retrospective molecular classification of potentially eligible patients (pts) for targeted or immunotherapy treatment (tx) using the prospective CUPISCO trial’s criteria

Date

29 Sep 2019

Session

Poster Discussion session - Basic science

Presenters

Jeffrey Ross

Citation

Annals of Oncology (2019) 30 (suppl_5): v851-v934. 10.1093/annonc/mdz394

Authors

J.S. Ross1, E.S. Sokol2, H. Moch3, L. Mileshkin4, G. Baciarello5, F. Losa6, A. Beringer7, M. Thomas7, S. Foser7, J. Elvin8, N. Danziger8, N. Ngo8, J.Y. Tse8, K. Killian1, D.X. Jin9, L.M. Gay1, A. Krämer10

Author affiliations

  • 1 Pathology Group, Foundation Medicine, Inc., 02141 - Cambridge/US
  • 2 Product Development, Foundation Medicine, Inc., 02141 - Cambridge/US
  • 3 Department Of Pathology And Molecular Pathology, University Hospital Zurich, 8091 - Zurich/CH
  • 4 Department Of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne/AU
  • 5 Department Of Medical Oncology, Institut Gustave Roussy, Villejuif/FR
  • 6 Medical Oncology Department, Hospital de Sant Joan Despí Moisès Broggi, Barcelona/ES
  • 7 Personalised Healthcare Oncology, Global Product Development Medical Affairs, F. Hoffmann-La Roche Ltd, Basel/CH
  • 8 Pathology Group, Foundation Medicine, Inc., Cambridge/US
  • 9 Product Development, Foundation Medicine, Inc., Cambridge/US
  • 10 Clinical Cooperation Unit Molecular Hematology/oncology And Department Of Internal Medicine V, German Cancer Research Center (DKFZ) and University of Heidelberg, Heidelberg/DE
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Resources

Abstract 4166

Background

Standard CUP therapy has not changed for decades. CUPISCO (NCT03498521) is an ongoing randomised prospective trial using CGP to assign CUP pts to individualised targeted or immunotherapy arms (molecularly guided therapy; MGT).

Methods

Archival tissue from 303 centrally reviewed undifferentiated- and adeno-CUP cases in the FoundationCore database underwent hybrid capture-based CGP (FoundationOne® CDx). Microsatellite instability (MSI), tumour mutational burden (TMB) and genomic loss of heterozygosity (gLOH) were calculated (Frampton Nat Biotechnol 2013; Swisher Lancet Oncol; Chambers Genome Med 2017). PD-L1 expression was measured by DAKO 22C3 immunohistochemistry. Pts were classified by whether CGP results could have informed assignment to CUPISCO arms; TTF-1+, CK7–/CK20+/CDX2+ or TMPRSS2:ERG+ cases were excluded.

Results

The sex ratio was 1:1; median age was 67 yrs (range 22–89+). CGP revealed 96 pts (32%) matched to a CUPISCO arm (Table).Table:

1983PD_PR

CUPISCO arm% Genomic alterations
Alectinib0.66
Vismodegib1.32
Ipatasertib8.25
Olaparib5.61
Erlotinib + bevacizumab2.31
Vemurafenib + cobimetinib2.97
Subcutaneous trastuzumab + pertuzumab + chemo9.24
Atezolizumab9.24
Entrectinib (in development)0.33

Conclusions

32% of CUP pts would have been potentially eligible for MGT in CUPISCO. Future studies including additional biomarkers, such as PD-L1–positivity and gLOH, may identify a greater proportion of CUP pts potentially benefitting from individualised treatment.

Clinical trial identification

Editorial acknowledgement

Support for third-party editing assistance for this abstract, furnished by Daniel Clyde, PhD, 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

J.S. Ross: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine, Inc.; Non-remunerated activity/ies, Support for third-party editing assistance: F. Hoffmann-La Roche Ltd. E.S. Sokol: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine, Inc; Non-remunerated activity/ies, Support for third-party editing assistance: F. Hoffmann-La Roche Ltd. H. Moch: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: F. Hoffmann-La Roche Ltd ; Advisory / Consultancy, Travel / Accommodation / Expenses: Definiens AG; Non-remunerated activity/ies, Support for third-party editing assistance: F. Hoffmann-La Roche Ltd. L. Mileshkin: Travel / Accommodation / Expenses: F. Hoffmann-La Roche Ltd; Travel / Accommodation / Expenses: Beigene; Non-remunerated activity/ies, Support for third-party editing assistance: F. Hoffmann-La Roche Ltd. G. Baciarello: Honoraria (self), Travel / Accommodation / Expenses: F. Hoffmann-La Roche Ltd; Honoraria (self), Travel / Accommodation / Expenses: Astellas; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Honoraria (self), Travel / Accommodation / Expenses: Ipsen; Honoraria (self): Amgen; Travel / Accommodation / Expenses: AstraZeneca; Non-remunerated activity/ies, Support for third-party editing assistance: F. Hoffmann-La Roche Ltd; Advisory / Consultancy, Travel / Accommodation / Expenses: Sanofi. F. Losa: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: F. Hoffmann-La Roche Ltd; Advisory / Consultancy, Speaker Bureau / Expert testimony: Sanofi; Advisory / Consultancy, Research grant / Funding (institution): Amgen; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck; Advisory / Consultancy: Servier; Non-remunerated activity/ies, Support for third-party editing assistance: F. Hoffmann-La Roche Ltd. A. Beringer: Full / Part-time employment, Non-remunerated activity/ies, Support for third-party editing assistance: F. Hoffmann-La Roche Ltd. M. Thomas: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment, Non-remunerated activity/ies, Support for third-party editing assistance: F. Hoffmann-La Roche Ltd. S. Foser: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment, Non-remunerated activity/ies, Support for third-party editing assistance: F. Hoffmann-La Roche Ltd. J. Elvin: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine, Inc; Non-remunerated activity/ies, Support for third-party editing assistance: F. Hoffmann-La Roche Ltd. N. Danziger: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine, Inc; Non-remunerated activity/ies, Support for third-party editing assistance: F. Hoffmann-La Roche Ltd. N. Ngo: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine, Inc; Non-remunerated activity/ies, Support for third-party editing assistance: F. Hoffmann-La Roche Ltd. J.Y. Tse: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine, Inc; Non-remunerated activity/ies, Support for third-party editing assistance: F. Hoffmann-La Roche Ltd. K. Killian: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine, Inc; Full / Part-time employment, Special Volunteer: National Cancer Institute; Shareholder / Stockholder / Stock options, Non-remunerated activity/ies, Support for third-party editing assistance: F. Hoffmann-La Roche Ltd. D.X. Jin: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine, Inc; Shareholder / Stockholder / Stock options, Non-remunerated activity/ies, Support for third-party editing assistance: F. Hoffmann-La Roche Ltd. L.M. Gay: Full / Part-time employment, Current: Ellem Consulting; Non-remunerated activity/ies, Support for third-party editing assistance: F. Hoffmann-La Roche Ltd; Full / Part-time employment, Previous: Foundation Medicine, Inc. A. Krämer: Honoraria (self), Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses, Non-remunerated activity/ies, Support for third-party editing assistance: F. Hoffmann-La Roche Ltd; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Daiichi Sankyo; Honoraria (self), Advisory / Consultancy: Abbvie; Honoraria (institution), Research grant / Funding (institution): Bayer; Advisory / Consultancy: BMS; Travel / Accommodation / Expenses: Celgene; Research grant / Funding (institution): Merck.

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