AstraZeneca’s Tagrisso (osimertinib) with the addition of pemetrexed and platinum-based chemotherapy has been approved in China for the 1st-line treatment of adult patients with locally advanced or metastatic epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) whose tumours have exon 19 deletions or exon 21 (L858R) mutations.
The approval by China’s National Medical Products Administration (NMPA) was based on the results from the FLAURA2 Phase III trial published in The New England Journal of Medicine and results from a prespecified exploratory subgroup analysis of efficacy and safety in Chinese patients, which was presented at the European Society for Medical Oncology (ESMO) Asia Congress 2023.
In the overall trial population, Tagrisso with the addition of chemotherapy reduced the risk of disease progression or death by 38 per cent by investigator assessment compared to Tagrisso monotherapy, which is the 1st-line global standard of care. Median progression-free survival (PFS) was 25.5 months for patients treated with Tagrisso plus chemotherapy, an 8.8-month improvement versus Tagrisso monotherapy (16.7 months).
PFS results by blinded independent central review (BICR) in the overall trial population were consistent with 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)
While the overall survival (OS) remained immature at the second interim analysis (41 per cent maturity), an encouraging trend towards an OS benefit was observed with Tagrisso plus chemotherapy versus Tagrisso alone. The trial continues to assess OS as a key secondary endpoint.
Efficacy results from the China cohort of FLAURA2 were broadly consistent with the overall trial. By investigator assessment, Tagrisso with the addition of chemotherapy reduced the risk of disease progression or death by 44 per cent compared to Tagrisso monotherapy. Median PFS was 27.4 months for patients treated with Tagrisso plus chemotherapy, a 5.1-month improvement versus Tagrisso monotherapy (22.3 months).
PFS results in the China cohort by BICR were consistent with the results by investigator assessment, showing 33.2 months median PFS with Tagrisso plus chemotherapy, an 11.2-month improvement over Tagrisso monotherapy (22 months).
A trend towards an OS benefit was also observed in the China cohort for Tagrisso plus chemotherapy versus Tagrisso alone. The safety profile of Tagrisso with the addition of chemotherapy was generally manageable and consistent with the established profiles of the individual medicines. Adverse event (AE) rates were higher in the Tagrisso plus chemotherapy arm, driven by well-characterised chemotherapy-related AEs. Discontinuation rates of Tagrisso due to AEs were 11 per cent for Tagrisso plus chemotherapy and 6 per cent for monotherapy.
Tagrisso is approved as monotherapy in more than 100 countries including the US, EU, China and Japan. Approved indications include 1st-line treatment of patients with locally advanced or metastatic EGFRm NSCLC, locally advanced or metastatic EGFR T790M mutation-positive NSCLC, and adjuvant treatment of early-stage EGFRm NSCLC. In addition to this new approval in China, Tagrisso with the addition of chemotherapy is also approved in the US and several other countries for 1st-line treatment of patients with locally advanced or metastatic EGFRm NSCLC.