Regardless of PD-L1 expression or histology, treatment with atezolizumab was associated with a clinically relevant improvement in overall survival compared with docetaxel in patients with previously treated non-small cell lung cancer (NSCLC), a study published in The Lancet has shown.1
Atezolizumab is a PD-L1 blocking monoclonal antibody that reinvigorates anticancer immunity by inhibiting PD-L1 and PD1. To evaluate the efficacy and safety of atezolizumab in patients with previously treated NSCLC, researchers designed the open-label, pivotal, phase 3 OAK trial (ClinicalTrials.gov Identifier: NCT02008227).
For the study, investigators enrolled 1225 adult patients with squamous or nonsquamous stage IIIB or IV NSCLC who had received 1 to 2 prior chemotherapy regimens, including 1 or more platinum-based combination therapies, for advanced disease. Participants were randomly assigned 1:1 to receive atezolizumab or docetaxel intravenously every 3 weeks.
In the primary analysis of 850 patients, results showed that treatment with atezolizumab significantly reduced the risk of death by 27% compared with docetaxel (hazard ratio [HR], 0.73; 95% CI, 0.62-0.87; P =.0003). Median overall survival was 13.8 months (95% CI, 11.8-15.7) with atezolizumab vs 9.6 months (95% CI, 8.6-11.2) with chemotherapy.
Among the 663 patients with 1% or greater PD-L1 on tumor cells or tumor-infiltrating immune cells, atezolizumab therapy significantly reduced the risk of death by 26% vs docetaxel (HR, 0.74; 95% CI, 0.58-0.93; P =.0102); median overall survival was 15.7 months (95% CI, 12.6-18.0) and 10.3 months (95% CI, 8.8-12.0), respectively.
In patients with low or undetectable PD-L1 expression, researchers found that atezolizumab therapy was associated with a similar risk reduction (HR, 0.75; 95% CI, 0.59-0.96). Median overall survival was 12.6 months in patients who received atezolizumab and 8.9 months in those given docetaxel.
The study further revealed that overall survival benefit was similar in patients with squamous (HR, 0.73; 95% CI, 0.54-0.98) or nonsquamous (HR, 0.73; 95% CI, 0.60-0.89) histology.
In addition, substantially fewer patients in the atezolizumab arm experienced treatment-related grade 3 to 4 adverse events vs the docetaxel arm (15% vs 43%). One patient in the docetaxel arm died to due to treatment-related respiratory tract infection.
Based on these findings, the US Food and Drug Administration approved atezolizumab for the treatment of patients with metastatic NSCLC whose disease progressed during or following platinum-containing chemotherapy.
1. Rittmeyer A, Barlesi F, Waterkamp D, et al. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet. 2016 Dec 12. doi: 10.1016/S0140-6736(16)32517-X. [Epub ahead of print]