1701O - Comprehensive Genomic Profiling (CGP) of Thymic Gland Carcinomas

Date 09 September 2017
Event ESMO 2017 Congress
Session Basic science
Topics Thymoma and Thymic Cancer
Lung and other Thoracic Tumours
Translational Research
Presenter Jeffrey Ross
Citation Annals of Oncology (2017) 28 (suppl_5): v595-v604. 10.1093/annonc/mdx391
Authors J.S. Ross1, P. Vanden Borre2, N. Almog2, A.B. Schrock3, J. Chung2, J. Vergilio4, J. Suh4, S. Ramkissoon4, E. Severson4, S. Daniel4, S.M. Ali4, V.A. Miller4, P.J. Stephens4, J.A. Elvin4, L.M. Gay2
  • 1Pathology, Albany Medical Center, 12208 - Albany/US
  • 2Pathology, Foundation Medicine, 02141 - Cambridge/US
  • 3Clinical Development, Foundation Medicine, MA 02141 - Cambridge/US
  • 4R & D, Foundation Medicine, 02141 - Cambridge/US

Abstract

Background

Thymic gland carcinomas include a variety of histologic subtypes with variable clinical aggressiveness and response to local and systemic therapies. We queried whether CGP could refine tumor subtypes and uncover new targeted and immunotherapy options for patients with relapsed and metastatic disease (mTC).

Methods

FFPE sections of 174 consecutive cases of mTC was sequenced using hybridization-captured, adaptor ligation-based libraries to a mean coverage depth of > 500X for up to 315 cancer-related genes plus 37 introns from 28 genes frequently rearranged in cancer. Total mutational burden (TMB) was determined on 1.1 Mb. Clinically relevant genomic alterations (CRGA) were defined as GA linked to drugs on the market or under evaluation in mechanism driven clinical trials.

Results

All mTC were clinically advanced and included 4% adenocarcinomas (TAC), 3% basaloid (TBC), 3% lymphoepitheliomatous (TLEC), 17% neuroendocrine (TNEC), 31% non-NE undifferentiated (TNOS), 40% squamous and 2% sarcomatoid (TSRC) carcinomas (Table). mTC were twice as common in men than women, had a peak incidence in late middle age, and featured an average of 4 GA/case and 0.9 CRGA/case. The most common molecular targets were KIT and PIK3CA. Other targets were PDGFRA, FGFR3, PTCH1, FBXW7, BRCA2, IDH1, ERBB2 and ERBB3. The more frequent subtypes (TNEC, TSCC and TNOS) tended to have more GA, with KIT targets in ∼ 10% of cases. Low TMB in mTC was common; only 6% of cases had >10 mut/Mb and 3% had >20 mut/Mb. Examples of mTC with responses to targeted therapies will be presented.Table:

1701O

TACTBCTLECTNECTNOSTSCCTSRC
Patients7553054694
Median Age (y)48585048575761
Gender43% F60% F20% F37% F24% F34% F50%F
GA/tumor4.02.81.03.34.14.14.8
CRGA0.90.300.90.81.01.0
Significant GAPDGFRA FGFR3 KIT MET PTCH1CDKN2A FBXW7CDKN2A MEN1KIT BRCA2 IDH1 ERBB2 ERBB3KIT PTEN PIK3CAKIT FGFR3 PIK3CAERBB2 IDH1 KIT
TMB >10 mut/Mb14%0%0%3%5%9%0%
TMB >20 mut/Mb0%0%0%3%5%9%0%

Conclusions

mTC histologic subtypes have varying GA and TMB status. The more common TSCC, TNEC and TNOS feature more GA, and when combined with TAC have more CRGA including KIT mutations and higher TMB. CGP shows promise to guide both targeted and immunotherapy selection for patients with this rare malignancy.

Clinical trial identification

Legal entity responsible for the study

Jeffrey S Ross

Funding

None

Disclosure

J.S. Ross, V.A. Miller, P.J. Stephens: Employee, leader and owns stock in Foundation Medicine. P. Vanden Borre, N. Almog, A.B. Schrock, J. Chung, J-A. Vergilio, J. Suh, S. Ramkissoon, E. Severson, S. Daniel, S.M. Ali, J.A. Elvin, L.M. Gay: Employee and owns stock in Foundation Medicine.