Regulatory Decision Summary for Tecentriq

This market authorization was based on one pivotal trial (OAK), and one main supportive trial (POPLAR) in patients with advanced or metastatic non-small cell lung cancer (NSCLC) who had experienced disease progression during or after a prior platinum-based chemotherapy regimen and where an additional line of therapy was allowed for patients with a known EGFR mutation or ALK translocation. Tecentriq demonstrated a clinically and statistically significant improvement in overall survival (OS) compared to docetaxel treated patients in both the pivotal and supportive trials.

The improvement in overall survival (OS) compared to docetaxel was 4.2 months (median OS) with a corresponding 27% reduction in the risk of death. However, patients with EGFR mutations did not show improved OS with atezolizumab compared to docetaxel. For the secondary endpoint of progression-free survival (PFS), the shape of the K-M curves appears consistent with a type of apparent delay in effect that can be observed clinically with immuno-oncology drugs.

In both trials, subjects were enrolled regardless of PD-L1 expression status and the pre-study PD-L1 expression status was used as a stratification factor. A survival benefit was observed regardless of PD-L1 expression status at baseline by all pre-defined expression levels in the all-comer populations studied. In aggregate, the studies are considered indicative of an all-comer treatment effect with significant OS benefit even among patients with low or no PD-L1 expression. Data from the studies suggest that patients whose tumours have the highest PD-L1 expression levels appear to be most likely to experience the greatest degree of benefit.

The safety profile was considered acceptable in the context of the treatment of metastatic NSCLC. Important identified risks associated with atezolizumab monotherapy are known to include immune-mediated adverse reactions such as pneumonitis, hepatitis, colitis, endocrinopathies (for example, hypophysitis, thyroid disorders), neuropathies and infusion reactions. The Product Monograph contains appropriate instructions for medication discontinuation, dose holding and corticosteroid treatment.

Overall the benefit/risk analysis is considered favourable for the use of Tecentriq in the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy (patients with EGFR or ALK genomic tumour aberrations should have disease progression on a therapy for these aberrations prior to receiving Tecentriq).