FDA Benefit‐Risk Assessment of Osimertinib for the Treatment of Metastatic Non‐Small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor T790M Mutation

: On March 30, 2017, the U.S. Food and Drug Administration (FDA) approved osimertinib for the treatment of patients with metastatic, epidermal growth factor receptor (EGFR) T790M mutation-positive, non-small cell lung cancer (NSCLC), as detected by an FDA-approved test, whose disease has progressed following EGFR tyrosine kinase inhibitor (TKI) therapy. Approval was based on demonstration of a statistically significant difference in the primary endpoint of progression-free survival (PFS) when comparing osimertinib with chemotherapy in an international, multicenter, open-label, randomized trial (AURA3). In this confirmatory trial, which enrolled 419 patients, the PFS hazard ratio for osimertinib compared with chemotherapy per investigator assessment was 0.30 (95% confidence interval 0.23-0.41), p  20%) in patients treated with osimertinib were diarrhea, rash, dry skin, nail toxicity, and fatigue. Herein, we review the benefit-risk assessment of osimertinib that led to regular approval, for patients with metastatic NSCLC harboring EGFR TKI whose disease has progressed on or after EGFR TKI therapy. IMPLICATIONS FOR PRACTICE: Osimertinib administered to metastatic non-small cell lung cancer (NSCLC) patients harboring an EGFR T790M mutation, who have progressed on or following EGFR TKI therapy, demonstrated a substantial improvement over platinum-based doublet chemotherapy as well as durable intracranial responses. The ability to test for the T790M mutation in plasma using the FDA-approved cobas EGFR Mutation Test v2 (Roche, Basel, Switzerland) identifies patients with NSCLC tumors not amenable to biopsy. Since a 40% false-negative rate has been observed with the circulating tumor DNA test, re-evaluation of the feasibility of tissue biopsy is recommended to identify patients with a false-negative plasma test result who may benefit from osimertinib.