TAGRISSO (osimertinib) - Non-small cell lung cancer (NSCLC)

The Committee considers that the clinical benefit of TAGRISSO (osimertinib) remains substantial only as monotherapy for adjuvant treatment after complete tumour resection and after adjuvant chemotherapy if indicated for adult patients with stage IB – IIIA non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) activating mutations by exon 19 deletion or exon 21 substitution (L858R).

In view of:

• evidence of superiority of osimertinib (TAGRISSO), in a randomised double-blind phase III study, versus placebo in terms of disease-free survival previously noted in the inclusion registration opinion;
• new overall survival data providing evidence of superiority of osimertinib on this outcome measure:
  • in stage II-IIIA patients (hierarchical secondary endpoint), HR= 0.49; CI95% [0.33; 0.73], and
  • in stage IB-IIIA patients (total population, (hierarchical secondary endpoint), HR= 0.49; CI95% [0.34; 0.70];

and despite:

• uncertainties as to the effect size of osimertinib on the overall survival outcome measure related to the risk of overestimation of the gain in overall survival (disproportion between the groups of patients receiving osimertinib after recurrence [27.2% in the placebo group and 40.8% in the osimertinib group] – while it has had a marketing authorisation at the locally advanced and metastatic stages since 2018 – giving rise to suboptimal treatment of patients in the placebo group in cases of recurrence);
• a decrease in the long-term effect size observed in relation to the findings submitted for the inclusion review of 2022, suggested in the analysis with 22.1 additional months of follow-up;
• increased toxicity versus placebo with in particular more grade ≥ 3 adverse events (20.2% versus 13.4%) or adverse events resulting in treatment discontinuation (11% versus 2.9%);
• the lack of probative quality-of-life data;

the Committee deems that, based on the data currently available, TAGRISSO (osimertinib), as adjuvant treatment, provides moderate clinical added value (CAV III) in relation to the current therapeutic strategy for stage IB-IIIA NSCLC with EGFR activating mutations by exon 19 deletion or exon 21 substitution (L858R) after complete tumour resection and adjuvant chemotherapy if indicated.