TAGRISSO

What it is

TAGRISSO is osimertinib mesilate tablets. Each film-coated tablet contains either 40 mg or 80 mg of osimertinib as the mesilate salt. Osimertinib is an orally administered tyrosine kinase inhibitor and a selective and irreversible inhibitor of Epidermal Growth Factor Receptors harbouring single or double mutations common in non-small cell lung cancer.

Approved indications

— Adjuvant therapy after tumour resection in patients with non-small cell lung cancer whose tumours have activating EGFR mutations, as detected by a validated test. — Treatment of patients with locally advanced, unresectable (stage III) NSCLC whose tumours have activating EGFR mutations and whose disease has not progressed during or following platinum-based chemoradiation therapy. — First-line treatment of patients with locally advanced or metastatic NSCLC whose tumours have activating EGFR mutations, as detected by a validated test. — Treatment of patients with locally advanced or metastatic NSCLC that is EGFR T790M mutation-positive, as detected by a validated test. — In combination with pemetrexed and platinum-based chemotherapy for first-line treatment of patients with locally advanced or metastatic NSCLC whose tumours have EGFR exon 19 deletions or exon 21 L858R mutations.

Dosing overview

The recommended dose of TAGRISSO for monotherapy is 80 mg tablet once a day. The recommended dose when taken in combination with pemetrexed and platinum-based chemotherapy is 80 mg osimertinib once a day. TAGRISSO can be taken without regard to food at the same time each day, and the tablets should be swallowed whole with water. Patients in the adjuvant setting should receive treatment until disease recurrence or unacceptable toxicity, or for a total of three years. Patients with locally advanced or metastatic lung cancer should receive TAGRISSO treatment until disease progression or unacceptable toxicity. If dose reduction is necessary, the dose of TAGRISSO should be reduced to 40 mg taken once daily.

Key safety warnings

Interstitial Lung Disease or ILD-like adverse events were reported in 4.0% and were fatal in 0.4% of 1813 patients who received TAGRISSO monotherapy in clinical studies. TAGRISSO should be withheld and promptly investigated for ILD in any patient who presents with worsening respiratory symptoms indicative of ILD such as dyspnoea, cough and fever, and should be permanently discontinued if ILD is confirmed. Severe cutaneous reactions including erythema multiforme and life-threatening reactions such as Stevens-Johnson syndrome or toxic epidermal necrolysis have been reported with TAGRISSO, often with blisters or mucosal lesions, and treatment should be interrupted if severe bullous, blistering or exfoliative conditions develop. Prolongation of the heart rate-corrected QT interval occurs in patients treated with TAGRISSO. Periodic monitoring with electrocardiograms and electrolytes should be considered in patients with congestive heart failure, electrolyte abnormalities, or those taking medications known to prolong the QTc interval. Left Ventricular Ejection Fraction decreases greater than or equal to 10 percentage points and a drop below 50% occurred in 4.2% of patients treated with TAGRISSO monotherapy, and in a placebo-controlled trial 1.5% of patients treated with TAGRISSO experienced such decreases. In patients with cardiac risk factors and those with conditions that can affect LVEF, cardiac monitoring including assessment of LVEF at baseline and during treatment should be considered. Rare reports of aplastic anaemia have been reported in association with TAGRISSO treatment, and some cases had a fatal outcome. Patients should be advised of signs and symptoms including persistent fever, bruising, bleeding, pallor, infection and fatigue, and if these develop, close patient monitoring and drug interruption or discontinuation should be considered.

Contraindications

Hypersensitivity to the active substance or to any of the excipients is a contraindication. Strong CYP3A inducers are contraindicated. The safety and efficacy of TAGRISSO in children or adolescents aged less than 18 years have not been established.

PBS listing

TAGRISSO osimertinib 40 mg and 80 mg tablets are registered on the ARTG, both first listed on 3 August 2016. TAGRISSO has been recommended by PBAC for multiple indications including T790M mutation-positive NSCLC, first-line treatment of EGFR mutation-positive NSCLC, adjuvant therapy in Stage IB to IIIA EGFR mutation-positive NSCLC after surgical resection, and unresectable locally advanced (Stage III) EGFR mutation-positive NSCLC whose disease has not progressed following platinum-based chemoradiation therapy.

Regulatory history

TAGRISSO was first listed on the ARTG on 3 August 2016 for both 40 mg and 80 mg strengths. In November 2014, PBAC recommended TAGRISSO for treatment of locally advanced or metastatic NSCLC with EGFR T790M mutation in patients who had progressed on or after prior EGFR TKI therapy. In November 2017, PBAC recommended an amendment to allow osimertinib to be used as first-line therapy for locally advanced or metastatic EGFR T790M mutation-positive NSCLC. In July 2020, PBAC recommended a change for first-line treatment of Stage IIIB or Stage IV EGFR mutation-positive NSCLC. In November 2023, PBAC recommended a new listing for adjuvant therapy after surgical resection of Stage IB to IIIA EGFR mutation-positive NSCLC. In July 2025, PBAC recommended TAGRISSO for unresectable locally advanced (Stage III) EGFR mutation-positive NSCLC whose disease has not progressed during or following platinum-based chemoradiation therapy.