194O - Hybrid-Capture Based Comprehensive Genomic Profiling of Hepatocellular Carcinoma Identifies Patients Who May Benefit from Targeted Therapies and Im...

Date 19 November 2017
Event ESMO Asia 2017 Congress
Session Gastrointestinal tumours 2
Topics Anti-Cancer Agents & Biologic Therapy
Hepatobiliary Cancers
Cancer Immunology and Immunotherapy
Gastrointestinal Cancers
Translational Research
Presenter James Suh
Citation Annals of Oncology (2017) 28 (suppl_10): x57-x76. 10.1093/annonc/mdx660
Authors J. Suh1, E. Severson1, J. Hechtman2, G. Frampton3, D. Fabrizio3, J. Sun3, S. Ali4, P. Gu5, S. Klempner6, V. Miller7, P. Stephens3, J. Ross8
  • 1Pathology, Foundation Medicine, Inc., 27560 - Morrisville/US
  • 2Pathology, Memorial Sloan Kettering Cancer Center, 10021 - New York/US
  • 3Cancer Genomics, Foundation Medicine, Inc., 02142 - Cambridge/US
  • 4Clinical Development, Foundation Medicine, Inc., 02142 - Cambridge/US
  • 5Medical Oncology, New York University Langone Medical Center, 10016 - New York/US
  • 6Medical Oncology, The Angeles Clinic and Research Institute/Cedars-Sinai Medical Center, Los Angeles/US
  • 7Medical Affairs, Foundation Medicine, Inc., 02142 - Cambridge/US
  • 8Pathology, Foundation Medicine, Inc., 02142 - Cambridge/US

Abstract

Background

Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide and shows minimal response to existing chemotherapies. Tumor mutational burden (TMB) and microsatellite instability (MSI) are predictive biomarkers of response to immune checkpoint inhibitors. Comprehensive genomic profiling (CGP) is a hybrid capture-based next-generation sequencing (NGS) test that may help optimize therapy regimens for advanced stage HCC patients.

Methods

CGP of up to 315 cancer-related genes was performed on 614 consecutive cases of hepatocellular carcinoma (2012-16) using a hybrid-capture, adaptor ligation based NGS assay and genomic alterations (GA: point mutations, small indels, copy number changes and rearrangements) were recorded. TMB was calculated from up to 1.1 megabase (Mb) of cancer genome as the number of somatic, coding point mutations and indels per Mb (low:

Results

In 614 HCC, the median age was 61 years and 70% were male. HBV/HCV infection status was not available. The most frequent GA occurred in TERT (51%), TP53 (34%), CTNNB1 (32%), MALT1 (14%), PASK (14%), CD36 (14%), MYC (13%), ARID1A (12%), CDKN2A (8.5%) and RB1 (7.6%). Potentially targetable GA involved CCND1 (5.5%), FGF19 (5.1%), FGF3/4 (4.2%), MET (2.0%), ERBB2 (1.1%), EGFR (0.7%), BRAF (0.5%) and ALK (0.4%). TMB was low in 394 (64%), intermediate in 214 (35%) and high in 6 (1.0%) patients. Of 378 patients with available MSI status, 1 HCC was MSI-H; GA involving MLH1 (0.4%), MSH2 (0.4%), MSH6 (1.1%) and POLE (0.2%) were also detected. Clinical examples of responders to everolimus and nivolumab will be presented.

Conclusions

CGP of HCC reveals rarer GA and small subsets of patients with high TMB and MSI that may open new avenues of medical treatment for select advanced HCC as well as understudied, recurrently altered genes such as PASK and MALT1, suggesting a role in the management of advanced-stage HCC.

Clinical trial identification

Legal entity responsible for the study

Foundation Medicine, Inc.

Funding

None

Disclosure

J. Suh, E. Severson, G. Frampton, D. Fabrizio, J. Sun, S. Ali, V. Miller, P. Stephens, J. Ross: Foundation Medicine (employment, equity). All other authors have declared no conflicts of interest.