183P - Frequency of actionable fusions in 7,735 patients with solid tumors

Background

Identifying rare oncogenic gene fusions can be challenging. Comprehensive genomic profiling (CGP) approaches that include RNA sequencing can improve fusion detection versus exome or targeted DNA sequencing alone. Here, we characterize gene fusions in solid tumors detected with the OncoExTra^TM tumor-normal, whole-exome (WES), whole-transcriptome (WTS) CGP assay.

Methods

The study included oncology patients with solid tumor samples tested with the OncoExTra assay between May 2018 and November 2022. We quantified the frequency of all potentially clinically-relevant fusions, including those with therapeutic, clinical trial eligibility, prognostic or diagnostic implications, and the subset of these with FDA-approved therapies at the time of testing.

Results

Overall, 7,735 patients and 33 tumor types were included. We identified 931 (12.0%) patients with clinically-relevant fusions, 224 (2.9%) of whom had a fusion associated with an FDA-approved therapy, with large variation in frequency across tumor types (Table). Sarcomas had one of the highest proportions (34.4%) of fusions identified, many of which are diagnostic or prognostic: PAX3/7-FOXO1 (n=17), SS18-SSX (n=10), CIC-DUX4 (n=8), and MDM2 (n=6). We also detected fusions in 189 (9.5%) breast (including 43 with ESR1, 13 with ERBB2, 12 with FGFR family), 33 (3.4%) colorectal (including 5 RSPO, 3 RET), and 29 (9.9%) non-small cell lung (including 10 ALK, 5 RET, 3 ERBB2) cancer patients. Across all cancers, ERG (3.0%) was the most common fusion partner, found predominantly in prostate cancer patients. Other notable fusions involved ESR1 (n=64); RAF family (n=30); NTRK family (n=27); and RSPO family (n=12).

Conclusions

Oncogenic gene fusions, including those with FDA-approved therapies, were identified with varying frequency across solid tumors. Sarcomas had a high proportion of fusions, including those with therapeutic, diagnostic and prognostic relevance. Table: 183P

Gene fusions in select tumor types

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Exact Sciences Corporation.

Funding

Exact Sciences Corporation.

Disclosure

J.R. Hoag, C. Flannery, D. Hall, M.C. Evans, A. Akkunuri, S. Thakkar, J.R. Lobello, G.D. Basu: Financial Interests, Personal, Full or part-time Employment: Exact Sciences. S.B. Gruber: Financial Interests, Personal, Ownership Interest: Brogent International. All other authors have declared no conflicts of interest.