An Immune Checkpoint Inhibitor for Patients with Platinum-Ineligible NSCLC

Pivotal trials support the use of PD-L1 inhibitors, with or without chemotherapy, as the standard-of-care first-line treatment for patients with advanced-stage non–small-cell lung cancer (NSCLC), but these studies have excluded patients ineligible for platinum-based doublet chemotherapy. As a result, many patients ineligible for platinum-based chemotherapy continue to receive single-agent chemotherapy. To compare possible treatments in this population, researchers conducted a manufacturer-funded, phase 3, open-label international trial in 453 patients who had stage IIIB or stage IV NSCLC lacking EGFR or ALK alterations. The investigators considered the patients unsuitable for platinum-doublet chemotherapy because they had an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or 3, or they were at least 70 years old and had substantial comorbidities or contraindications.

The patients were randomized in a 2:1 ratio to atezolizumab 1200 mg every 3 weeks or to one of two chemotherapies — vinorelbine or gemcitabine in 3-weekly or 4-weekly cycles. The primary endpoint was overall survival. Treatment with atezolizumab was associated with significantly longer overall survival compared with single-agent chemotherapy (10.3 months vs. 9.2 months; stratified hazard ratio, 0.78). Moreover, 2-year survival was 24% with atezolizumab, double the rate with chemotherapy (12%). No new safety signals were seen with atezolizumab, and the incidence of treatment-related adverse events (grade 3 or 4) was half that seen in the chemotherapy arm (16% and 33%).