125P - Targeted methylation sequencing of plasma cell-free DNA identifies patients with advanced breast, colorectal, non-small cell lung cancer, melanoma...

Date 11 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Cancer in Adolescents
Biomarkers
Breast Cancer
Colon Cancer
Rectal Cancer
Lung and other Thoracic Tumours
Melanoma and other Skin Tumours
Translational Research
Presenter Adam Jassowicz
Citation Annals of Oncology (2017) 28 (suppl_5): v22-v42. 10.1093/annonc/mdx363
Authors A. Jassowicz1, L. Liu2, H. Huang1, D.S. Hong1, A. Naing1, V. Subbiah1, S.A. Piha-Paul1, J. Toung2, R. Vijayaraghavan2, R. Zhang2, H. Kang2, S. Fu1, A.M. Tsimberiodou1, C. Lu3, C. Eng4, S. Moulder5, S. Kopetz6, R. Amaria7, F. Meric-Bernstam1, F. Janku1
  • 1Department Of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, 77030 - Houston/US
  • 2Oncology, Illumina, Inc., San Francisco/US
  • 3Department Of Thoracic/head And Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, 77030 - Houston/US
  • 4Department Of Gastrointestinal (gi) Medical Oncology, The University of Texas MD Anderson Cancer Center, 77030 - Houston/US
  • 5Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston/US
  • 6Gi Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston/US
  • 7Department Of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 77030-4095 - Houston/US

Abstract

Background

Plasma cell-free DNA (cfDNA) sampling from patients with advanced cancers offers a minimally invasive source of tumor DNA for molecular testing, including methylation profiling. Tumor sequencing at disease progression offers insights into cancer biology, but is often not done because of logistical and other challenges associated with tumor biopsies.

Methods

Plasma samples were collected from patients with advanced breast, colorectal, non-small cell lung cancer (NSCLC) and melanoma at the time of disease progression and/or on therapy. Up to 30 ng (median 18ng) of plasma cfDNA was tested with the pan-cancer methylation panel to target a total of 10,888 CpG sites using an Illumina HiSeq2500 sequencer to calculate methylation scores. Methylation scores were correlated with cancer types and clinical outcomes.

Results

Of 69 plasma cfDNA samples collected from patients (colorectal cancer, 28; NSCLC, 18, breast cancer, 12; melanoma, 11) at disease progression, methylation scores were consistent with the presence of cancer in 84% (58/69); while in 79% (46/58) of plasma cfDNA samples, methylation scores accurately classified the underlying cancer type. High methylation scores in plasma cfDNA samples collected at disease progression compared to low methylation scores were associated with shorter survival irrespective of the tumor type (3.9 vs 10.4 months, P 

Conclusions

Methylation scores from plasma cfDNA collected at disease progression from patients with advanced cancers accurately classify underlying cancer types and are associated with survival, TTF and RECIST responses.

Clinical trial identification

MD Anderson Protocols laboratory protocols LAB10-0334 and PA13-0956

Legal entity responsible for the study

MD Anderson Cancer Center

Funding

Sidney Kimmel Foundation for Cancer Research (Filip Janku); Sheikh Khalifa Al Nahyan Ben Zayed Institute for Personalized Cancer Therapy (Filip Janku); National Center for Advancing Translational Sciences (grant no. UL1 TR000371); National Institutes of Health through MD Anderson’s Cancer Center Support Grant (P30 CA016672); Illumina.

Disclosure

L. Liu, J. Toung, R. Vijayaraghavan, R. Zhang, H. Kang: Employee and stock ownership Illumina, Inc. F. Janku: Scientific Advisory Boards: Illumina, Guardant Health; Paid consulting: Trovagene; Stocks: Trovagene. All other authors have declared no conflicts of interest.