Atezolizumab (Tecentriq®) in previously treated non-small cell lung cancer (NSCLC)

Atezolizumab, a monoclonal antibody, is an immune checkpoint inhibitor. By inhibiting the programmed death ligand 1 (PD-L1), atezolizumab enables T-cell activation, restoring their ability to effectively detect and destroy tumour cells. The US Food and Drug Administration (FDA) recently approved atezolizumab for the treatment of patients with metastatic NSCLC, whose disease progressed during or following platinum-based chemotherapy. Patients who progress following treatment for epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumour aberrations may also receive atezolizumab. The approval was based on two international, randomized, open-label trials, OAK (phase III) and POPLAR (phase II). OAK evaluated the comparative efficacy and safety of atezolizumab versus docetaxel in a total of 1,225 NSCLC patients after failure with platinum-based chemotherapy. Atezolizumab increased the primary endpoint of overall survival (OS) in the intention-to-treat (ITT) population by 4.2 months and duration of response (DOR) by 10.1 months, compared with docetaxel. Patients with higher PD-L1 expression derived the greatest improvement in median OS (+ 11.6 months) with atezolizumab, 20.5 months versus 8.9 months with docetaxel. Atezolizumab did not improve progression-free survival (PFS) or the proportion of patients with an objective response (OR) compared with docetaxel. While fewer patients had treatment-related AEs with atezolizumab compared to docetaxel, clinically significant immune-related AEs were reported including pneumonitis, hepatitis, colitis and thyroid disease. Overall, with the exception of those with EGFR mutations, atezolizumab increases OS and DOR in previously treated NSCLC patients regardless of PD-L1 expression or histology, with a favourable safety profile compared to docetaxel. There is no evidence regarding quality of life, patient reported outcome measures or patient reported experience measures to determine whether atezolizumab provides clinically significant improvement in the symptoms or severity of NSCLC. Results from OAK hold limited external validity as participants are not entirely generalisable to clinical practice. Longer trials are needed which directly compare the safety and efficacy of atezolizumab versus other immunotherapies such as nivolumab or pembrolizumab, or docetaxel in combination with nintedanib or ramucirumab.