Abstract 1905
Background
The Neurotrophic Tyrosine Kinase genes, NTRK1-3 are extremely rare drivers of a wide variety of malignancies. The recent pan-cancer approval of kinase inhibitor drugs targeting NTRK has sparked interest in the frequency of NTRK rearrangements found in NSCLC.
Methods
Comprehensive genomic profiling (CGP) was performed on FFPE samples from 42,791 NSCLC cases. Tumor mutational burden (TMB) was determined on 0.8-1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined on 95 loci.
Results
58 (0.1%) of the NSCLC featured genomic fusions or rearrangements in the NTRK1-3 genes (Table). The ages and genders of NTRK1-3 fusion+ cases were similar to NSCLC in general and did not enrich for younger patients. NTRK fusions were highest in adenocarcinomas (67%) and squamous cell carcinomas (SCC; 9%). The average genomic alterations (GA) per NTRK1-3 altered tumor ranged from 6.1 – 8.2 GA and was higher than that reported for EGFR, ALK and ROS1 driven NSCLC. The NTRK1-3 fusions involved a wide variety of fusion partners with NTRK1- IRF2BP2 (6) and NTRK1-TPM3 (9) most frequent. The levels of TMB and frequencies of PD-L1 expression were higher than EGFR, ALK and ROS1 altered cases. The STK11 GA frequencies were similar to NSCLC in general but lower than the frequency in lung adenocarcinoma only.Table:
1549P
NTRK1 | NTRK2 | NTRK3 | |
---|---|---|---|
Cases | 47 | 5 | 6 |
Median age/Range | 64 (22-88) | 68 (65-76) | 71 (63-74) |
Gender m/f | 23/24 | 3/2 | 5/1 |
NSCLC Types Adenocarcinoma NSCLC NOS Large Cell Neuroendocrine SCC Sarcomatoid Large Cell | 31 10 2 2 1 1 | 4 1 | 4 2 |
GA/tumor | 6.1 | 8.2 | 6.2 |
TP53 | 55% | 80% | 67% |
KRAS | 15% | 0% | 17% |
STK11 | 11% | 20% | 0% |
MSI High | 0% | 0% | 0% |
Median TMB mut/Mb | 3.5 | 11.3 | 14.4 |
TMB >10/20 mut/Mb | 22%/7% | 60%/20% | 67%/33% |
PD-L1 Expression low/high | 32%/16% (n = 19) | 50%/50% (n = 2) | 0%/33% (n = 3) |
Conclusions
Although the addition of RNA sequencing may marginally increase their detection, based on this DNA-only CGP sequencing study, NTRK1-3 fusions are extremely rare in NSCLC. These NTRK1-3 fusion-driven NSCLC differ from other well-known driver associated NSCLC such as EGFR, ALK and ROS1 in their having higher GA/tumor, TMB and PD-L1 expression frequencies suggesting that immunotherapies may also be available for the care of these patients, possibly as a combination therapy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Foundation Medicine.
Funding
Foundation Medicine.
Disclosure
E.S. Sokol: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. S.E. Trabucco: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. D.X. Jin: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. G.M. Frampton: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. J.A. Elvin: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. J. Vergilio: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. J.K. Killian: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. N. Ngo: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. D. Lin: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. S. Ramkissoon: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. E. Severson: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. S.M. Ali: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. A.B. Schrock: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. J. Chung: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. P. Reddy: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. K. McGregor: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. B.M. Alexander: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment, Officer / Board of Directors: Foundation Medicine. J.S. Ross: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. All other authors have declared no conflicts of interest.
Resources from the same session
4228 - Clinical Evaluation of Drug-Eluting Bead Transcatheter Arterial Chemoembolization(D-TACE) versus Conventional TACE in Treatment of unresectable Hepatocellular Carcinoma
Presenter: Yi Chen
Session: Poster Display session 1
Resources:
Abstract
3930 - Safety profile of tepotinib in patients with advanced solid tumors: pooled analysis of phase I and II data
Presenter: Thomas Decaens
Session: Poster Display session 1
Resources:
Abstract
5373 - Drug-drug interaction profile of tepotinib with CYP3A and P-gp substrates
Presenter: Juergen Heuer
Session: Poster Display session 1
Resources:
Abstract
5455 - Bioavailability of tepotinib: impact of omeprazole and food
Presenter: Juergen Heuer
Session: Poster Display session 1
Resources:
Abstract
2618 - Tislelizumab Exposure-Response Analyses of Efficacy and Safety in Patients with Advanced Tumors
Presenter: Chi-Yuan Wu
Session: Poster Display session 1
Resources:
Abstract
2563 - Population Pharmacokinetics of Tislelizumab in Patients with Advanced Tumors
Presenter: Chi-Yuan Wu
Session: Poster Display session 1
Resources:
Abstract
2021 - The Addition of Metformin to Systemic Anticancer Therapy
Presenter: Jung Han Kim
Session: Poster Display session 1
Resources:
Abstract
5243 - Growth modulation index (GMI) as a comparative measure of clinical activity of larotrectinib versus prior systemic treatments in adult and pediatric TRK fusion cancer patients
Presenter: Antoine Italiano
Session: Poster Display session 1
Resources:
Abstract
598 - Analysis of the overall survival and main surrogates used for FDA approvals in solid and hematological malignancies.
Presenter: Maria Kleniewska-Wieczor
Session: Poster Display session 1
Resources:
Abstract
5381 - Comparison of intratumoral docetaxel exposure in cancer patients between nanoparticle entrapped docetaxel (CPC634) and conventional docetaxel (Cd): the CriTax study
Presenter: Ruben Van Eerden
Session: Poster Display session 1
Resources:
Abstract