P3.02b-106 Local Experience of Osimertinib Use; Retrospective Review Based on Plasma EGFR Using ddPCR Technique: Topic: EGFR RES

Abstract

Osimertinib was approved by FDA in Nov 2016 for treatment of patients with metastatic EGFR-T790M mutation positive NSCLC, as detected by an FDA-approved test (Cobas ® EGFR Mutation Test v2) after EGFR-TKI failure, with an ORR up to 70% and a PFS around 11 months. We report local experience on EGFR mutations detected by droplet digital polymerase chain reaction (ddPCR) technique on cell free tumor DNA from lung cancer patients, guiding osimertinib therapy after 1st or 2nd generation TKI failure. All patients with plasma EGFR testing done using ddPCR technique from Nov 2015 to Mar 2016 are retrospectively identified and analyzed. 47 patients were tested for EGFR mutations by ddPCR after EGFR TKI failure. 19 patients had detectable T790M mutant copies of 3.5 - 65887.3 mutant copies/ml plasma (median 61.5). All had previous use of TKI > 6 months (range 171 – 1592 day, median 544). Among the 14 patients who received osimertinib, the median PFS and OS were not reached over a mean follow up of 4.3 months. There was one progressive disease, five stable diseases and eight partial responses as the best treatment response. The number of T790M mutant copies number/ml plasma in the PR group was numerically higher than the SD/PD group (mean 416.5 vs 25.9) but statistically insignificant (p-value 0.15) for difference. Of the limited eight patients having simultaneous tissue biopsy and molecular testing in this cohort, six was concordant with the plasma EGFR result. The two remaining had detectable T790M in plasma EGFR but not in tissue re-biopsy, and, of note, one achieved partial response and one stable disease after osimertinib. Plasma-EGFR-directed osimertinib treatment using ddPCR technique is feasible. The technique quantifies mutant load with potential prognostic implication, and detects heterogeneous tumors who might benefit from osimertinib despite negative tissue biopsy result.