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

Updated: Jun 05, 2020
  • 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 fully approved osimertinib for patients with EGFR T79M-positive NSCLC whose disease progressed on or after EGFR TKI therapy. In April 2018, the FDA also approved osimertinib for the first-line treatment of patients with metastatic NSCLC whose tumors express EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test. [161, 162]

Approval was based on a phase III FLAURA study conducted in 556 patients with EGFR exon 19 deletion or exon 21 L858R mutation-positive, unresectable or metastatic NSCLC who had not received previous systemic treatment for advanced disease. Patients were randomized to receive osimertinib or a standard EGFR-TKI (gefitinib or erlotinib). Of those randomized to the standard EGFR-TKIs, 20% received osimertinib as the next line of antineoplastic therapy. The estimated median PFS was 18.9 months in the osimertinib arm and 10.2 months in the standard EGFR-TKI arms. The ORR was 77% for the osimertinib arm and 69% with standard EGFR-TKI. The estimated median response durations for the osimertinib and standard therapy arms were 17.6 and 9.6 months, respectively. [163]

In patients with stage IB-IIIA NSCLC whose tumors express EGFR exon 19 deletions or exon 21 L858R mutations, the phase III ADAURA trial demonstrated that adjuvant therapy with osimertinib was associated with a nearly 80% reduction in the risk of disease recurrence or death. ADAURA compared osimertinib treatment with placebo in patients with localized or locally advanced NSCLC that had been completely resected with negative margins. [164]

In patients with stage II to IIIA disease, median disease-free survival (DFS) was not reached for patients in the osimertinib arm, but was 20.4 months for patients in the placebo arm (HR, 0.17; P < 0.0001). In the overall study population, including patients with stage IB disease, median DFS was not reached for patients in the osimertinib arm but was 28.1 months for patients in the placebo arm (HR, 0.21; P < 0.0001). The trial was unblinded early and halted on the recommendation of the independent data-monitoring committee, due to the efficacy of osimertinib. [164]

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