Abstract 5366
Background
Larotrectinib is the first therapy approved in the U.S. for locally advanced or metastatic solid tumors with neurotropic tyrosine receptor kinase (NTRK) gene fusions. NTRK gene fusions have been documented with variable frequency across numerous tumor types; limited data exist regarding the relationship of NTRK gene fusions with other targetable biomarkers. This study evaluated the co-occurrence of NTRK gene fusions with other therapy molecular markers in cancer patients.
Methods
This retrospective study included cancer patients from a de-identified Flatiron Health-Foundation Medicine Clinico-Genomic Database (CGDB) who had next-generation sequencing (NGS) between Jan 2011 and July 2018. The co-occurrence frequencies of NTRK gene fusions with the following markers was determined using NGS assays including FoundationOne and FoundationOne Heme: tumor mutation burden (TMB), microsatellite instability (MSI), ALK, BRAF, ERBB2, EGFR, ROS1, and KRAS.
Results
An evaluable sample of 15,971 of 33,398 patients in the CGDB had one of 18 histologies where at least one NTRK fusion patient was identified. NTRK gene fusions were identified in 29 patients: 55% (16/29) were female; 69% (20/29) were Caucasians. The median age was 60 years (Q1-Q3: 49.0-65.0). Fifteen different fusion partners were identified; the most frequent were ETV6-NTRK3 (n = 8), TPM3-NTRK1 (n = 6), and TPR-NTRK1 (n = 3). Co-occurring genomic alterations are shown in the table.Table: 102P
Co-occurring biomarkers* | Patients with NTRK gene fusions (N = 29), % (n) |
---|---|
TMB High (>20 mut/mB) TMB Medium (<20, >5 mut/mB) | 20.7 (6/29) 10.3 (3/29) |
MSI (high) | 17.6 (3/17)** |
ALK rearrangement | 0.0 (0/29) |
BRAF alteration | 3.5 (1/29) |
ERBB2 amplification | 0.0 (0/29) |
EGFR alteration | 3.5 (1/29) |
ROS1 alteration | 0.0 (0/29) |
KRAS alteration | 10.3 (3/29) |
Variants of “known” or “likely” functional status were included
**MSI status missing for 12 patients
Conclusions
The study confirmed the rarity of NTRK gene fusions in cancer patients. Co-occurrence of the biomarkers ALK, BRAF, ERBB2, EGFR, ROS1, or KRAS was uncommon. These results highlight the importance of identifying patients with NTRK gene fusion-driven cancers, through molecular testing, who will benefit from the use of selective TRK kinase inhibitors across different solid tumors.
Clinical trial identification
Editorial acknowledgement
Michael Sheldon, PhD, of Scion, London, UK, funded by Bayer.
Legal entity responsible for the study
Bayer.
Funding
Bayer.
Disclosure
X. Jiao: Full / Part-time employment: Bayer. A. Lokker: Full / Part-time employment: Flatiron Health; Shareholder / Stockholder / Stock options: CVS Health, Roche, Medtronic, Sangamo Therapeutics. J. Snider: Full / Part-time employment: Flatiron Health; Shareholder / Stockholder / Stock options: Roche. E. Castellanos: Full / Part-time employment: Flatiron Health. S. Nanda: Full / Part-time employment: Bayer. V. Fisher: Full / Part-time employment: Foundation Medicine. J. Zong: Full / Part-time employment: Bayer. K. Keating: Full / Part-time employment: Bayer. M. Fellous: Full / Part-time employment: Bayer.
Resources from the same session
1868 - Evaluation and diagnostic potential of plasma biomarkers in bladder cancer
Presenter: Veronika Voronova
Session: Poster Display session 3
Resources:
Abstract
3655 - Liquid biopsy assays using combined circulating tumor cells and circulating tumor DNA in the same patients for the diagnosis of primary lung cancer
Presenter: Yongjoon Suh
Session: Poster Display session 3
Resources:
Abstract
3685 - Peripheral Cytotoxic T Cell Correlates with Tumor Mutational Burden and is Predictive for Progression Free Survival in Advanced Breast Cancer
Presenter: Xiao-ran Liu
Session: Poster Display session 3
Resources:
Abstract
1050 - Splenic Metabolic Activity as Biomarker in Cervical Cancer
Presenter: Emiel De Jaeghere
Session: Poster Display session 3
Resources:
Abstract
1413 - Identification of distinct subtypes revealing prognostic and therapeutic relevance in diffuse type gastric cancer
Presenter: Seon-Kyu Kim
Session: Poster Display session 3
Resources:
Abstract
2140 - Recurrence risk evaluation in stage IB/IIA gastric cancer with TP53 codon 72 polymorphisms
Presenter: Satoshi Nishizuka
Session: Poster Display session 3
Resources:
Abstract
1573 - Identification and validation of a prognostic 4 genes signature for hepatocellular carcinoma: integrated ceRNA network analysis
Presenter: Yongcong Yan
Session: Poster Display session 3
Resources:
Abstract
1196 - Plasma KIM-1 is associated with clinical outcomes after resection for localized renal cell carcinoma: A trial of the ECOG-ACRIN Research Group (E2805)
Presenter: Wenxin Xu
Session: Poster Display session 3
Resources:
Abstract
2657 - Prognostic immunoprofiling of muscle invasive bladder cancer (MIBC) patients in a multicentre setting
Presenter: Katharina Nekolla
Session: Poster Display session 3
Resources:
Abstract
4900 - Molecular profiling and prognostic significance of TP53 mutations in Diffuse Large B Cell Lymphoma: identifying a high-risk subgroup
Presenter: Yuan-Kai Shi
Session: Poster Display session 3
Resources:
Abstract