Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Proffered Paper - Translational research

82O - Genomic evolution of metastatic tumours under therapeutic pressure

Date

19 Sep 2020

Session

Proffered Paper - Translational research

Topics

Cancer Diagnostics;  Clinical Research;  Targeted Therapy;  Cancer Biology;  Translational Research

Tumour Site

Breast Cancer

Presenters

Joris Van De Haar

Citation

Annals of Oncology (2020) 31 (suppl_4): S274-S302. 10.1016/annonc/annonc266

Authors

J. Van De Haar1, L.R. Hoes2, P. Roepman3, E. Cuppen3, L.F. Wessels4, E.E. Voest1

Author affiliations

  • 1 Molecular Oncology And Immunology, Netherlands Cancer Institute/Antoni van Leeuwenhoek hospital (NKI-AVL), 1066 CX - Amsterdam/NL
  • 2 Molecular Oncology Dept., NKI-AVL - Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, 1066 CX - Amsterdam/NL
  • 3 Medical Department, Hartwig Medical Foundation, 1098XH - Amsterdam/NL
  • 4 Division Of Molecular Carcinogenesis, Netherlands Cancer Institute, 1066CX - Amsterdam/NL

Resources

Login to access the resources on OncologyPRO.

If you do not have an ESMO account, please create one for free.

Abstract 82O

Background

Whole genome sequencing (WGS) is a powerful tool to swiftly and comprehensively identify personalized anticancer treatment options. However, in metastatic cancer, the extent to which somatic genomic profiles are preserved between lesions (heterogeneity in space) and over the course of a patient’s anticancer treatment (heterogeneity in time) remains unclear. Clinicians need guidance on the necessity to repeat genomic characterization in patients with cancer in order to efficiently maximize treatment opportunities.

Methods

WGS data was prospectively collected of 497 longitudinally sampled biopsies from 239 metastatic cancer patients with tumours from 21 different primary sites. Biopsies were taken prior to and after various types of systemic treatments. Available clinical data was used to study associations between the evolution of somatic genomic profiles and clinical characteristics.

Results

During the biopsy interval (median 6.4 months, IQR 3.8-9.6 months), there was a statistically significant but modest (median <10%; mean <20%) increase in the number of mutations, copy number alterations, structural variants and indels. Genomic biomarkers for standard-of-care treatments and clinical trial enrolment could be identified in 22% (n=107) and 51% (n=253) of biopsies, respectively. For 99% (n = 247) of the sequential pairs, the second biopsy did not yield new information regarding standard-of-care genomic treatment indications. Out of 355 biomarkers for clinical trial enrolment identified in the first biopsies, 326 (92%) were also present in the subsequent biopsy. For 224 out of 250 (90%) paired biopsies, the second biopsy did not yield additional biomarkers for clinical trial enrolment. Twenty-eight of the 81 (35%) patients treated with targeted or hormonal therapy between the biopsies gained somatic variants within the gene directly targeted by the drug, revealing known and novel resistance mechanisms.

Conclusions

Our data demonstrates that a one-time WGS analysis during the disease course of a patient with metastatic cancer is (i) sufficient for identifying standard-of-care genomic biomarkers, and (ii) supportive of revealing investigational therapeutic targets that remain present at later stages of the disease.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Josephine Nefkens Stichting, Hartwig Medical Foundation, Oncode Institute, Center for Personalized Cancer Treatment.

Disclosure

All authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.