Tagrisso (osimertinib) - 4 indications

Scroll down for more information on each indication:

• for 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; approved November 2015
• for adjuvant therapy after tumor resection in adults with NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations; approved April 2018
• for 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; approved December 2020
• for use with the addition of chemotherapy for the treatment of adult patients with locally advanced or metastatic EGFRm NSCLC; approved February 2024

General Information

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.
• with the addition of chemotherapy for the treatment of adult patients with locally advanced or metastatic EGFR mutated NSCLC

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. 

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.

Side Effects

Adverse effects associated with the use of Tagrisso may include, but are not limited to, the following:

• leukopenia
• lymphopenia
• thrombocytopenia
• diarrhea
• anemia
• rash
• musculoskeletal pain
• nail toxicity
• neutropenia
• dry skin
• stomatitis
• fatigue
• cough

Indication 1 - 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

approved November 2015

Clinical Trial Results

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.

Indication 2 - adjuvant therapy after tumor resection in adults with NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations

approved April 2018

Clinical Trial Results

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.

Indication 3 - for 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

approved December 2020

Clinical Trial Results

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.

Indication 4 - with the addition of chemotherapy for EGFRm NSCLC

approved December 2020

Clinical Trial Results

Approval was based on FLAURA2: Tagrisso with the addition of chemotherapy reduced the risk of disease progression or death by 38% compared to Tagrisso monotherapy which is the 1st-line global standard of care (p<0.0001). Median progression-free survival (PFS) by investigator assessment was 25.5 months for patients treated with Tagrisso  plus chemotherapy, an 8.8-month improvement versus Tagrisso  monotherapy (16.7 months). PFS results from blinded independent central review (BICR) were consistent with the results by investigator assessment, showing 29.4 months median PFS with Tagrisso plus chemotherapy, a 9.5-month improvement over Tagrisso  monotherapy (19.9 months).