Multinational phase 2 trial of osimertinib for advanced non-small cell lung cancer with EGFR T790M mutation detected in circulating tumor DNA

EGFR T790M mutations drive resistance in 50% of patients with advanced non-small cell lung cancer (aNSCLC) who progress on first or second generation EGFR TKIs, but are sensitive to osimertinib. Tissue sampling is the gold-standard modality for T790M testing, but is invasive. The multinational phase 2 PLASMA trial evaluated efficacy of osimertinib for aNSCLC with sensitizing EGFR and T790M mutation detected in circulating tumor DNA (ctDNA) of patients progressing after at least one first or second generation TKI. In the ITT population, the ORR was 50.9% and the DCR was 84.5% with promising duration of response and progression-free survival, while the median overall survival was 1.63 years. Grade 3 or higher treatment-emergent adverse events were seen in 11% of patients. The authors conclude that osimertinib was active in aNSCLC harboring sensitizing EGFR and T790M mutations in ctDNA testing post first or second generation TKIs.