Functional Profiling of Oncogenic Mutations in Lung Cancer Patients (NCT02274025) - Interim Results

e20066 Background: A major advancement in the treatment of lung cancer patients is the use of EGFR inhibitors, which have shown clinical efficacy. Additionally, there are several FDA approved inhibitors of EGFR that can be used. One of the major issues in this respect is the use of the different drugs, and prediction of response. To address this issue we have initiated an observational trial to functionally profile patient EGFR mutations as well as collect clinical outcome data. The functional analysis was done using the NovellusDx Precision Cancer Analysis system (PCAS), which monitors the activity of signaling pathways by means of a transfected cell-based assay. A major advantage of this system is its capacity to identify oncogenic activity of mutations as well as their response to different types of drugs Methods: On trial, pts that are suspected to have lung cancer and are eligible for biopsy or surgical intervention were included. All samples were taken before the start of treatment. Of these, the mutational status of EGFR was verified by NGS. Patients positive for mutations were then analyzed using PCAS for their activity and their response to the targeted therapy used in the clinic were measured. Clinical response was observed by cross-sectional imaging Results: In the 23 pts enrolled so far, 4 (17%) were identified with an alteration in EGFR. These patients were treated with EGFR inhibitors (Tarceva, Gefitinib or Gilotrif). The clinical responses varied, and 2 of the patients, underwent additional EGFR therapy (Gilotrif or Tagrisso) after disease progression. All treatment decision were at physician’s choice only. When profiling the activity level of these mutations, the PCAS successfully identified the oncogenic mutations as well as their sensitivity and resistance to the different drugs used Conclusions: This study shows the importance of functional profiling of mutations, specifically in the case of multiple treatment options. We show that the activity profiles of the identified EGFR mutations vary, and that their sensitivity to different targeted therapies also differs. Importantly, the different sensitivities were also predictive of the resistance seen in the clinical outcome of the patients Clinical trial information: NCT02274025.