Currently Enrolling Trials
Tagrisso (osimertinib) is an EGFR-TKI, a targeted cancer therapy, designed to inhibit both the activating, sensitizing mutations (EGFRm), and T790M, a genetic mutation responsible to EGFR-TKI treatment resistance.
Tagrisso is specifically indicated for the following:
- as adjuvant therapy after tumor resection in adult patients with non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test;
- the first-line treatment of adult patients with metastatic NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test;
- the treatment of adult patients with metastatic EGFR T790M mutation positive NSCLC, as detected by an FDA-approved test, whose disease has progressed on or after EGFR TKI therapy.
Tagrisso is supplied as a tablet for oral administration. The recommended dose is 80 mg tablet once a day until disease progression or unacceptable toxicity. Tagrisso can be taken with or without food. If a dose is missed, do not make up the missed dose and take the next dose as scheduled.
The FDA approval of Tagrisso was based on the following trials:
AURA3, an open label, randomized Phase III study designed to assess the efficacy and safety versus platinum-based doublet chemotherapy in patients with EGFR T790M positive, locally advanced, or metastatic NSCLC who have progressed following prior therapy with an EGFR-TKI. The median duration of progression-free survival was significantly longer with osimertinib than with platinum therapy plus pemetrexed (10.1 months vs. 4.4 months). The objective response rate was significantly better with osimertinib (71%) than with platinum therapy plus pemetrexed (31%). Two phase II studies (AURA extension and AURA2) demonstrated efficacy in 411 EGFRm T790M NSCLC patients that had progressed on or after an EGFR TKI. In those trials, overall objective response rate (ORR) was 59%. In a separate part of the AURA Study in 63 patients, ORR was 51% and median duration of response was 12.4 months.
ADAURA, a randomized, double-blind, placebo-controlled trial for the adjuvant treatment of patients with EGFR exon 19 deletions or exon 21 L858R mutation-positive NSCLC who had complete tumor resection, with or without prior adjuvant chemotherapy. Patients (n=682) were randomized (1:1) to receive Tagrisso 80 mg orally once daily or placebo following recovery from surgery and standard adjuvant chemotherapy if given. Patients who did not receive adjuvant chemotherapy were randomized within 10 weeks and patients who received adjuvant chemotherapy were randomized within 26 weeks following surgery. The major efficacy outcome measure was disease-free survival (DFS, defined as reduction in the risk of disease recurrence or death) in patients with stage II – IIIA NSCLC determined by investigator assessment. At 24 months, 90% of the patients with stage II to IIIA disease in the osimertinib group and 44% of those in the placebo group were alive and disease-free. In the overall population, 89% of the patients in the osimertinib group and 52% of those in the placebo group were alive and disease-free at 24 months.
FLAURA, a randomized, multicenter, double-blind, active controlled trial in 556 patients with EGFR exon 19 deletion or exon 21 L858R mutation-positive, metastatic NSCLC, who had not received previous systemic treatment for metastatic disease. Patients were randomized (1:1) to receive Tagrisso 80 mg orally once daily or to receive gefitinib 250 mg orally once daily or erlotinib 150 mg orally once daily until disease progression or unacceptable toxicity. The median overall survival was 38.6 months in the osimertinib group and 31.8 months in the comparator group. At 3 years, 79 of 279 patients (28%) in the osimertinib group and 26 of 277 (9%) in the comparator group were continuing to receive a trial regimen; the median exposure was 20.7 months and 11.5 months, respectively.
Adverse effects associated with the use of Tagrisso may include, but are not limited to, the following:
- dry skin
- nail toxicity
Mechanism of Action
Tagrisso (osimertinib) is kinase inhibitor of the epidermal growth factor receptor (EGFR), which binds irreversibly to certain mutant forms of EGFR (T790M, L858R, and exon 19 deletion) at approximately 9-fold lower concentrations than wild-type.
For additional information regarding Tagrisso or EGFR T790M mutation positive non-small cell lung cancer, please visit the Tagrisso website.