What is the role of osimertinib (Tagrisso) in the treatment of non–small cell lung cancer (NSCLC)?

Updated: Jul 15, 2021
  • Author: Winston W Tan, MD, FACP; Chief Editor: Nagla Abdel Karim, MD, PhD  more...
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Osimertinib (Tagrisso) is an irreversible EGFR-TKI inhibitor designed to inhibit both EGFR-sensitizing and EGFR T790M-resistance mutations, with clinical activity against CNS metastases. In March 2017, FDA approved osimertinib for EGFR T79M-positive NSCLC in patients whose disease progressed on or after EGFR TKI therapy.. [163]

Efficacy was demonstrated in the open-label AURA3 trial in which previously treated EGFR T790M mutation-positive metastatic NSCLC patients (n=419) received either osimertinib or platinum-based doublet chemotherapy. PFS significantly improved in the osimertinib arm compared to chemotherapy. No statistically significance in OS in either arm.

In April 2018, osimertinib was also approved for first-line treatment of metastatic NSCLC in patients whose tumors express EGFR exon 19 deletions or exon 21 L858R mutations.

Approval was based on a phase III FLAURA study conducted in 556 previously untreated patients with EGFR exon 19 deletion or exon 21 L858R mutation, metastatic NSCLC. Patients either received osimertinib or a standard EGFR-TKI (gefitinib or erlotinib). The osimertinib arm demonstrated statistically significant improvements in PFS and OS (18.9 months. 38.6 months) compared to the standard therapy arm (10.2 months, 31.8 months). [163, 164]

Osimertinib was also approved as an adjuvant therapy for NSCLC patients whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations following tumor resection.

Approval was based on the results from phase III ADAURA trial trial in which stage II to IIIA patients (n=682) were randomized to osimertinib or placebo. Differences in DFS in the overall study population were 11% DFS events in osimertinib arm compared to 46% in the placebo arm. Median DFS was not reached after 2 years in both the stage II-IIIA and overall population. Overall survival data was immature at the time of analysis. [165]

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