Regulatory Decision Summary for Tagrisso

AstraZeneca Canada Inc. has filed this priority Supplemental New Drug Submission (SNDS, 243288) to update the Tagrisso (osimertinib mesylate) Product Monograph with a new indication as adjuvant therapy after tumour resection in patients with non-small cell lung cancer (NSCLC) whose tumours have epidermal growth factor receptor (EGFR) mutations, based on the results from the pivotal trial D5164C00001 (ADAURA).

Following review, the indication approved is:

Tagrisso (osimertinib) is indicated as adjuvant therapy after tumour resection in patients with stage IB-IIIA non-small cell lung cancer (NSCLC) whose tumours have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations.

• A validated test is required to identify EGFR mutation-positive status prior to treatment.

The present submission is for use of Tagrisso (osimertinib) as adjuvant therapy after tumour resection in patients with non-small cell lung cancer (NSCLC) whose tumours have epidermal growth factor receptor (EGFR) mutations. This was supported by the ADAURA trial, an ongoing phase 3, double blind, randomized, placebo-controlled study. The study was designed to assess the efficacy and safety of osimertinib versus placebo in patients with stage IB-IIIA NSCLC with a centrally confirmed EGFR mutation (Ex19del and/or L858R, either alone or in combination with other EGFR mutations), who have undergone complete tumor resection, with or without postoperative adjuvant chemotherapy. In the study 682 patients were randomized to receive 1:1 osimertinib (80 mg once daily), or matching placebo. Planned treatment duration was for 3 years, or until disease recurrence or a treatment discontinuation criterion was met. The primary endpoint of the study was Disease Free Survival (DFS) in Stage II-IIIA population. The primary endpoint of DFS and the secondary endpoint of overall survival (OS) were tested in a subset of patients with stage II-IIIA disease, as well as in the overall population (IB/II/IIIA). Based on the study's hierarchical design, DFS in the overall population (stages IB/II/IIIA) was to be evaluated if statistical significance for DFS in the II/IIIA population was met.

The independent data monitoring committee (IDMC) made recommendations to unblind the study 2 years earlier than planned and complete the primary reporting because of a benefit signal seen for patients treated with osimertinib. The primary endpoint results (DFS in Stage II-IIIA) showed a statistically significant and clinically meaningful 83% reduction in the risk of disease recurrence or death for patients randomized to osimertinib compared with patients randomized to placebo with a hazard ration (HR) of 0.17 (99.06% CI: 0.11, 0.23, p < 0.0001).

The DFS HR for the overall population (including patients with stage IB) was 0.20 (99.12% CI: 0.14, 0.30, p < 0.0001), demonstrating a statistically significant and clinically meaningful 80% reduction in the risk of disease recurrence or death for patients randomized to osimertinib compared with patients randomized to placebo. The benefit of osimertinib is deemed to be evident in patients with stages IB-IIIA. The OS results are immature at this time.

The safety profile of omersitinib in the ADAURA trial remains consistent with that from previous trials. Decreases in neutrophil, platelet, lymphocyte and leukocyte counts are considered known adverse reactions for osimertinib. No new signal was observed. The benefit-risk profile is deemed to be positive for the approved adjuvant indication.