Osimertinib: A Review in Completely Resected, Early-Stage, EGFR Mutation-Positive NSCLC

Osimertinib (TAGRISSO (R)) is an orally administered, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that is approved for the adjuvant treatment of adults with completely resected, stage IB-IIIA, EGFR sensitizing mutation (exon 19 deletion or exon 21 [L858R] substitution)-positive non-small cell lung cancer (NSCLC). In the pivotal ADAURA trial in adults with completely resected, early-stage, EGFR mutation-positive (EGFRm+) NSCLC, osimertinib adjuvant therapy significantly prolonged disease-free survival (DFS) compared with placebo in the overall population of patients with stage IB-IIIA disease, as well as in the primary population of patients with stage II-IIIA disease. A DFS benefit of osimertinib was seen irrespective of whether or not patients received prior adjuvant chemotherapy. Overall survival (OS) data were very immature at the time of the analysis of DFS, and more mature OS data are awaited with interest. Osimertinib adjuvant therapy did not adversely affect health-related quality of life and was generally well tolerated, with a manageable safety profile and no new safety signals identified. Based on the available evidence, osimertinib is thus an appropriate targeted option for the adjuvant treatment of adults with completely resected, stage IB-IIIA, EGFRm+ NSCLC. Plain Language Summary Almost a third of patients with non-small cell lung cancer (NSCLC) have early-stage disease at diagnosis. Surgical resection is the primary treatment option, with adjuvant chemotherapy also recommended for select individuals with stage IB disease and those with stage II-IIIA disease. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are oral drugs that target and inhibit cancer-driving EGFR sensitizing mutations when present in patients with NSCLC. Osimertinib (TAGRISSO (R)) is the first EGFR TKI to be approved for adjuvant use in adults with completely resected, stage IB-IIIA, EGFR mutation-positive (EGFRm+) NSCLC. In a trial in the intended patient population, adjuvant osimertinib reduced the risk of disease recurrence or death by approximate to 80% versus placebo, regardless of whether or not patients received adjuvant chemotherapy. The effect of adjuvant osimertinib on overall survival is being evaluated. The safety profile of osimertinib in the early-stage disease setting was consistent with that seen in the advanced disease setting. Based on the available evidence, osimertinib is an appropriate targeted option for the adjuvant treatment of adults with completely resected, stage IB-IIIA, EGFRm+ NSCLC.