78P - Real-world analysis of actionable gene fusions identified by NGS and correlation with IHC in 422 patients from the community

Background

Detecting oncogenic gene fusions that can be effectively targeted in a tumor type agnostic manner have been shown to transform patient care. Unfortunately, however, patients in certain community settings may only be tested for NTRK fusions following a positive IHC screen result. Here we compared the gap between panTRK IHC testing and NGS fusion confirmation for NTRK or additional fusions.

Methods

8307 clinical samples across 33 tumor types were tested for RNA fusions using a CLIA grade hybrid capture RNA-seq based fusionome-like assay. De-identified results were analyzed for either the 19 actionable fusion genes (ALK, BRAF, FGFR1-4, MET, NOTCH1/2, NRG1, NTRK1-3, PDGFB, PDGFRA/B, RAF1, RET and ROS1) or only for NTRK fusions. Pan-NTRK IHC results on fusion positive patients were analyzed. Data was analyzed according to an IRB-approved protocol.

Results

When we analyzed the NGS results, we detected a targetable fusion in 5.1% (n=422) patients. Of those 104 had a NTRK1/2/3/ fusion (38/10/56). The additional 3.8% patients had other therapy candidate fusions: ALK (0.6%), BRAF 0.3%, FGFRs 0.9%, MET 0.4%, NOTCH2 0.2%, NRG1 0.2%, PDGFRA 0.1%, RAF1 0.2%, RET 0.5%, ROS1 0.2%, excluding NTRK positive cases. Only 2 patients were positive for an NTRK fusion and an additional actionable fusion. From a total of 221 patients with actionable fusions by NGS, IHC was positive on 70% (51/73) of the NTRK fusion positive patients. Moreover, NTRK expression by IHC was found on 91% of NTRK1 and 100% of NTRK2, but only on 44% of the NTRK3 positive cases by NGS. Conversely, only 54% of the pan-TRK IHC positive patients expressed a NTRK fusion transcript while 46% expressed other RNA fusions, primarily FGFRs (20 %) ALK (4%) and ROS1 (4%).

Conclusions

The data demonstrates that up to 4 -fold more patients could have a fusion matched therapy when testing for 19 druggable fusions as compared to testing only for NTRK fusions or following IHC testing. Pan NTRK IHC failed to detect half of NTRK3 fusions. The data suggests that simultaneous detection of several actionable fusions by NGS can increase the therapeutic options for cancer patients in community settings.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

H. Husain: Financial Interests, Personal, Speaker, Consultant, Advisor: Neogenomics. N. Montgomery, R. Puentes, D. Lyle: Financial Interests, Personal, Full or part-time Employment: Neogenomics. F. Lopez-Diaz: Financial Interests, Personal, Full or part-time Employment: Neogenomics; Financial Interests, Personal, Stocks/Shares: Neogenomics. All other authors have declared no conflicts of interest.