Atezolizumab in non-squamous non-small cell lung cancer

Immune therapy opened a new era in treatment of advanced non-small cell lung cancer (NSCLC).Immune checkpoint inhibitors (ICIs) targeting the programmed deathligand 1 (PD-L1)/programmed death-1 (PD-1) pathway have achieved great success over conventional cytotoxic chemotherapy.Several anti-PD-1 antibodies, including nivolumab and pembrolizumab, were approved by the Food and Drug Administration (FDA) in 2015 for use as second-line therapy for advanced NSCLC.The drugs were approved after demonstrating both clinical efficacy and an improved safety profile compared with standard docetaxel for the treatment of non-squamous NSCLC (1,2).Pembrolizumab received FDA approval in 2016 as a firstline treatment for patients with advanced NSCLC and high PD-L1 expressing tumors (3,4).The PD-L1 antibody, atezolizumab (Tecentriq, F. Hoffmann-La Roche/Genentech), is a selective humanized monoclonal IgG1 antibody, which was designed to block the interaction between PD-L1 and the PD-1/B7-1 activation complex, but not bind to PD-L2 (5).This antibody showed efficacy in the open-label randomized phase III OAK trial (NCT02008227) which led to its approval as a secondline therapy for advanced NSCLC (6).Efficacy was noted in both squamous and non-squamous NSCLC subsets and regardless of PD-L1 status (6).However, efficacy of ICIs in patients with NSCLC harboring epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) rearrangement was controversial in previous trials (1,2,6).Following the OAK trial, the phase III IMpower150 study evaluating atezolizumab for first-line treatment was initiated and the results were published in the New England Journal Medicine (7).The aim of this trial was to compare the efficacy and safety of atezolizumab in combination with carboplatin and paclitaxel with or without bevacizumab in patients with stage IV non-squamous NSCLC who had not previously received chemotherapy.A total of 1,202 patients were enrolled and randomized (1:1:1) to receive: atezolizumab plus carboplatin and paclitaxel (ACP group); atezolizumab and bevacizumab plus carboplatin and paclitaxel (ABCP group); bevacizumab plus carboplatin and paclitaxel (BCP group).The entire intention-to-treat population (ITT) was divided into two groups: patients with a wild-type genotype (ITT-WT; patients without EGFR or ALK alterations); or patients with EGFR or ALK alterations (ITT-EGFR/ALK+).Within the ITT-WT group, patients with high expression of an effector T-cell (Teff) gene signature in the tumor were categorized as Teff-high WT population.PD-L1 expression was evaluated by SP142 antibody.The two primary end points were progression-free survival (PFS) in ITT-WT and Teff-high WT populations, and overall survival (OS) in the ITT-WT population.In addition, the following key secondary end points were assessed: PFS and OS in the ITT-EGFR/ALK+ group; PFS in the PD-L1 expression subgroups; toxicity in the ITT group.