PS01.66: Biomarker Stratification of Outcomes of Third-Generation EGFR TKI Therapy in Patients with Previously-Treated Advanced NSCLC: Topic: Medical Oncology.

EGFR mutation status identifies patients with NSCLC who experience significantly better outcomes on TKI therapy versus standard platinum-doublet therapy. A subset of patients will have de novo resistance and acquired resistance is expected for all patients. The EGFR T790M mutation is the mechanism of resistance at progression in as many as 60% of patients. Third generation EGFR TKIs maintain activity following T790M-mediated resistance and have been studied following progression on first- or second-generation EGFR TKI therapy. One of those agents, rociletinib, had a confirmed overall response rate (ORR) of 34% in patients with T790M positive tumors (Goldman et al. J Clin Oncol. 2016(34):15_suppl 9045). Here we investigated the VeriStrat® test, a commercially-available proteomic blood test, to explore its ability to stratify patients with EGFR mutation-positive tumors treated with rociletinib according to their outcomes. Pre-treatment blood samples were collected from centrally confirmed T790M positive patients enrolled in TIGER-X, a phase 1/2 study evaluating rociletinib in patients with at least one prior EGFR TKI therapy, and TIGER-2, a phase 2 registration trial for patients who had progressed on their first and only EGFR TKI therapy. A 237 patient subset from the new drug application filing was available for analysis. Of those samples, 230 were evaluable with the VeriStrat test (2 samples yielded indeterminate results and 5 failed quality control review). Patient blood samples were analyzed using standard VeriStrat processing and categorized as VSGood or VSPoor. ORR and progression-free survival (PFS) were the primary endpoints of this analysis. Study participants had ECOG performance status of 0 (n=60), 1 (n=169), or 2 (n=1). In the patients included in this analysis, all had tumors with centrally confirmed T790M mutations. Of the evaluable patients, 73.5% had a VSGood status (n=169) and 26.5% had a VSPoor status (n=61). ORR in VSGood patients (32.5%, 95% CI: 25.4-39.6%) was not significantly different in VSPoor patients (31.3%, 95% CI: 19.5-42.7%). However, patients with a VSGood status had median PFS of 5.5 months versus 3.0 months in patients with a VSPoor status (HR=0.5, p< 0.0001). Although no significant difference was seen in ORR between VSGood and VSPoor patients treated with rociletinib, VSGood patients had significantly better PFS compared with VSPoor patients. These results support further investigation of proteomic, blood-based testing for potential benefit from third-generation TKI therapies in this patient population.