Abstract 2270
Background
Epidermal growth factor receptor (EGFR) inhibitors have shown efficacy in treating EGFR mutation-positive (EGFR+) non-small cell lung cancer (NSCLC). However, selecting EGFR inhibitors is challenging due to differential responses between pts and resistance mutations. We profiled EGFR mutations and their response to EGFR inhibitors using the Functional Annotation for Cancer Treatment (FACT) platform, which characterizes mutations by monitoring the activity of signaling pathways, via a transfected cell-based assay. As a functional platform, FACT reveals activation regardless of prior knowledge of a specific mutation.
Methods
The study included pts with suspected lung cancer undergoing biopsy/resection. EGFR mutational status was verified by NGS. Using the FACT platform, we analyzed the oncogenic signaling activity of EGFR mutations in these pts and response to physician chosen EGFR inhibitors compared to observed clinical responses assessed by cross-sectional imaging.
Results
Of 23 pts enrolled thus far, 4 pts were EGFR+ and 3 were treated with EGFR inhibitors (erlotinib, gefitinib, afatinib, AZD9291). The first pt had a complex EGFR mutation (T638M/E709A/L858R) and initially responded to erlotinib and after metastatic PD was treated with afatinib. The second pt had two alterations (exon 19 deletion/T790M) failed gefitinib and switched to AZD9291 with good response. The third patient had a common (L858R) mutation treated with erlotinib with good response. In all three pts, FACT assessed oncogenic signaling of the mutations and predicted responsiveness to EGFR inhibitors in accordance with observed clinical outcomes.
Conclusions
This study highlights the utility of functionally profiling mutations, specifically in cases where multiple treatment options are available. We demonstrate that measured signaling activity of the EGFR mutations tested and sensitivity to different targeted therapies was correlated with clinical outcomes in these pts.
Clinical trial identification
NCT02274025
Legal entity responsible for the study
N/A
Funding
NovellusDx
Disclosure
B. Miron, G. Tarcic, Z. Barbash, O. Edelheit, M. Vidne: NovellusDx. N. Peled: NovellusDx.
All other authors have declared no conflicts of interest.