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ePoster Display

1804P - Baseline mutational profiles of patients (pts) with carcinoma-of-unknown-primary-origin (CUP) enrolled onto CUPISCO

Date

16 Sep 2021

Session

ePoster Display

Presenters

Christoph Benedikt Westphalen

Citation

Annals of Oncology (2021) 32 (suppl_5): S1227-S1236. 10.1016/annonc/annonc681

Authors

C.B. Westphalen1, A. Karapetyan2, A. Beringer3, T. Bochtler4, N. Chalabi3, N. Cook5, G. Duran-Pacheco6, S. Golding7, E. Höglander8, F. Losa9, L. Mileshkin10, H. Moch11, C. Pauli11, J. Ross12, E. Sokol13, R. Tothill14, A. Krämer4

Author affiliations

  • 1 Comprehensive Cancer Center Munich & Department Of Medicine Iii, Ludwig Maximilian University of Munich, 81377 - Munich/DE
  • 2 Product Development Data Sciences, F. Hoffmann-La Roche Ltd, 4053 - Basel/CH
  • 3 Product Development Medical Affairs, F. Hoffmann-La Roche Ltd, 4053 - Basel/CH
  • 4 Molecular Hematology/oncology, German Cancer Research Center (DKFZ) and University of Heidelberg, Heidelberg/DE
  • 5 Medical Oncology, The University of Manchester and the Christie NHS Foundation Trust, Manchester/GB
  • 6 Biostatistics, F. Hoffmann-La Roche Ltd, 4053 - Basel/CH
  • 7 Statistics, F. Hoffmann-La Roche Ltd, 4053 - Basel/CH
  • 8 Oncology Biomarker Development - Gred, F. Hoffmann-La Roche Ltd, 4053 - Basel/CH
  • 9 Medical Oncology, Hospital de Sant Joan Despí-Moisès Broggi, ICO Hospitalet, Barcelona/ES
  • 10 Medical Oncology, Peter MacCallum Cancer Centre, Melbourne/AU
  • 11 Pathology, University of Zürich and University Hospital Zürich, 8091 - Zurich/CH
  • 12 Departments Of Pathology And Urology, Foundation Medicine, Inc./SUNY Upstate Medical University, Cambridge/Syracuse/US
  • 13 Cancer Genomics Research, Foundation Medicine, Inc., Cambridge/US
  • 14 Clinical Pathology, University of Melbourne, Melbourne/AU
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Abstract 1804P

Background

NCCN guidelines consider next-generation sequencing important in guiding therapeutic decision-making in CUP. CUPISCO (NCT03498521) is an ongoing, phase II randomised study of targeted therapy/cancer immunotherapy vs platinum-based chemotherapy in pts with unfavourable CUP, defined per ESMO guidelines. We present a preliminary, descriptive molecular analysis of ∼50% of pts designated for enrolment.

Methods

Upon enrolment, comprehensive genomic profiling, including determination of microsatellite instability and tumour mutational burden (TMB), was performed on formalin-fixed, paraffin-embedded tissues using the F1CDx assay. Gene alterations (GAs) found in ≥3% of pts were analysed using multiple correspondence analyses and hierarchical clustering to identify co-occurrences.

Results

Median age was 61.5 years (n = 346 [Apr 2021]; range: 22–84); median TMB was 2.5 mutations/Mb (0–63.0). In our analysis, 30% of patients carried a potentially targetable GA. Most frequent GAs were TP53 (44%), CDKN2A (32%), KRAS (21%; 2% G12C alterations), CDKN2B (21%), ARID1A (13%), STK11 (13%), MTAP (12%), PIK3CA (10%), MYC (8%), PBRM1 (8%), BAP1 (8%) and FGFR2 (8%). Beyond PIK3CA and FGFR2, other targetable GAs were identified in EGFR (2%), ERBB2 (6%), ALK (0.3%), ROS1 (1%), MET (2%), NTRK1 (1%) and BRAF (6%). The frequency of microsatellite instability and TMB-high (>16 mutations/Mb) samples was 3% and 9%, respectively. Based on hierarchical clustering of co-mutational profiles, multiple clusters were identified in the study cohort, each characterised by specific GA co-occurrences.

Conclusions

This descriptive analysis sheds further light on the molecular landscape in pts with poor-prognosis CUP. Our analyses demonstrate that CUP cases can be clustered based on molecular profiling; further studies are needed to determine if these clusters carry clinical relevance. Our early results suggest that comprehensive genomic profiling of CUP samples identifies therapeutically relevant GAs in a significant proportion of patients and could thus guide personalised treatment of these tumours.

Clinical trial identification

NCT03498521.

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

C.B. Westphalen: Financial Interests, Personal, Other, Honoraria: Bayer; Financial Interests, Personal, Other, Honoraria: Celgene; Financial Interests, Personal, Other, Honoraria: Ipsen; Financial Interests, Personal, Other, Honoraria: Servier; Financial Interests, Personal, Other, Honoraria: Taiho; Financial Interests, Personal, Other, Honoraria: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Advisory Role: Celgene; Financial Interests, Personal, Advisory Role: Shire/Baxalta; Financial Interests, Personal, Advisory Role: Rafael Pharmaceuticals; Financial Interests, Personal, Advisory Role: RedHill BioPharma; Financial Interests, Personal, Advisory Role: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Other, Travel/accommodation expenses: Bayer; Financial Interests, Personal, Other, Travel/accommodation expenses: Celgene; Financial Interests, Personal, Other, Travel/accommodation expenses: RedHill BioPharma; Financial Interests, Personal, Other, Travel/accommodation expenses: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Other, Travel/accommodation expenses: Servier; Financial Interests, Personal, Other, Travel/accommodation expenses: Taiho; Non-Financial Interests, Personal, Research Grant, Third party medical writing support: F. Hoffmann-La Roche Ltd. A. Karapetyan: Financial Interests, Personal, Full or part-time Employment, Employee: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Research Grant, Third party medical writing support: F. Hoffmann-La Roche Ltd. A. Beringer: Financial Interests, Personal, Full or part-time Employment, Employee: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Research Grant, Third party medical writing support: F. Hoffmann-La Roche Ltd. T. Bochtler: Financial Interests, Institutional, Research Grant, Institutional research funding: F. Hoffmann-La Roche Ltd; Financial Interests, Institutional, Other, Works as study oncologist for the CUPISCO trial: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Research Grant, Third party medical writing support: F. Hoffmann-La Roche Ltd. N. Chalabi: Financial Interests, Personal, Full or part-time Employment, Employee: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Research Grant, Third party medical writing support: F. Hoffmann-La Roche Ltd. N. Cook: Financial Interests, Personal and Institutional, Advisory Board: RedX Pharmaceuticals; Non-Financial Interests, Personal, Research Grant, Third party medical writing support: F. Hoffmann-La Roche Ltd; Financial Interests, Institutional, Research Grant, Research funding: AstraZeneca; Financial Interests, Institutional, Research Grant, Research funding: Orion; Financial Interests, Institutional, Research Grant, Research funding: F. Hoffmann-La Roche Ltd; Financial Interests, Institutional, Research Grant, Research funding: Taiho; Financial Interests, Institutional, Research Grant, Research funding: GSK; Financial Interests, Institutional, Research Grant, Research funding: Novartis; Financial Interests, Institutional, Research Grant, Research funding: Starpharma; Financial Interests, Institutional, Research Grant, Research funding: Bayer; Financial Interests, Institutional, Research Grant, Research funding: Eisai; Financial Interests, Institutional, Research Grant, Research funding: UCB; Financial Interests, Institutional, Research Grant, Research funding: RedX Pharmaceuticals; Financial Interests, Institutional, Research Grant, Research funding: Stemline Therapeutics; Financial Interests, Institutional, Research Grant, Research funding: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant, Research funding: Merck; Financial Interests, Institutional, Research Grant, Research funding: Tarveda Therapeutics. G. Duran-Pacheco: Financial Interests, Personal, Full or part-time Employment, Employee: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Research Grant, Third party medical writing support: F. Hoffmann-La Roche Ltd. S. Golding: Financial Interests, Personal, Full or part-time Employment, Employee: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Research Grant, Third party medical writing support: F. Hoffmann-La Roche Ltd. E. Höglander: Financial Interests, Personal, Full or part-time Employment, Employee: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Research Grant, Third party medical writing support: F. Hoffmann-La Roche Ltd. F. Losa: Financial Interests, Institutional, Research Grant, Institutional research funding: F. Hoffmann-La Roche Ltd; Financial Interests, Institutional, Research Grant, Institutional research funding: Amgen; Financial Interests, Institutional, Research Grant, Institutional research funding: Merck; Financial Interests, Personal, Other, Travel/accommodation expenses: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Other, Travel/accommodation expenses: Merck; Financial Interests, Personal, Advisory Board: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Servier; Financial Interests, Personal, Speaker’s Bureau: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Expert Testimony: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Speaker’s Bureau: Sanofi; Financial Interests, Personal, Expert Testimony: Sanofi; Non-Financial Interests, Personal, Research Grant, Third party medical writing support: F. Hoffmann-La Roche Ltd. L. Mileshkin: Financial Interests, Personal, Other, Travel/accommodation/expenses: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Other, Travel/accommodation/expenses: BeiGene; Non-Financial Interests, Personal, Research Grant, Third party medical writing support: F. Hoffmann-La Roche Ltd. H. Moch: Financial Interests, Institutional, Advisory Board, Advisory consultant: F. Hoffmann-La Roche Ltd; Financial Interests, Institutional, Advisory Board, Advisory consultant: Definiens; Financial Interests, Institutional, Advisory Board, Advisory consultant: Bayer; Financial Interests, Institutional, Advisory Board, Advisory consultant: Ipsen; Financial Interests, Institutional, Advisory Board, Advisory consultant: Amgen; Financial Interests, Personal, Other, Travel/accommodation/expenses: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Other, Travel/accommodation/expenses: Definiens; Financial Interests, Institutional, Research Grant, Institutional research funding: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Research Grant, Third party medical writing support: F. Hoffmann-La Roche Ltd. C. Pauli: Financial Interests, Personal, Other, Travel/accommodation/expenses: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Research Grant, Third party medical writing support: F. Hoffmann-La Roche Ltd. J. Ross: Financial Interests, Personal, Other, Honoraria: Foundation Medicine, Inc.; Financial Interests, Personal, Stocks/Shares: Foundation Medicine, Inc.; Financial Interests, Personal, Other, Leadership: Foundation Medicine, Inc.; Non-Financial Interests, Personal, Research Grant, Third party medical writing support: F. Hoffmann-La Roche Ltd. E. Sokol: Financial Interests, Personal, Full or part-time Employment, Employee: Foundation Medicine, Inc.; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Research Grant, Third party medical writing support: F. Hoffmann-La Roche Ltd. R. Tothill: Non-Financial Interests, Personal, Research Grant, Third party medical writing support: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Advisory Board, Honoraria: Merck-Serono Australia. A. Krämer: Financial Interests, Personal, Other, Honoraria: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Other, Leadership role: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Other, Honoraria: Daiichi Sankyo; Financial Interests, Personal, Other, Honoraria: AbbVie; Financial Interests, Institutional, Other, Honoraria: F. Hoffmann-La Roche Ltd; Financial Interests, Institutional, Other, Honoraria: Bayer; Financial Interests, Institutional, Research Grant, Institutional research funding: Merck; Financial Interests, Institutional, Research Grant, Institutional research funding: Bayer; Financial Interests, Personal, Other, Travel/accommodation/expenses: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Other, Travel/accommodation/expenses: Celgene; Financial Interests, Personal, Other, Travel/accommodation/expenses: Daiichi Sankyo; Financial Interests, Institutional, Advisory Board, Advisory consultant: F. Hoffmann-La Roche Ltd; Financial Interests, Institutional, Advisory Board, Advisory consultant: Daiichi Sankyo; Financial Interests, Institutional, Advisory Board, Advisory consultant: BMS; Financial Interests, Institutional, Advisory Board, Advisory consultant: AbbVie; Non-Financial Interests, Personal, Research Grant, Third party medical writing support: F. Hoffmann-La Roche Ltd.

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