Atezolizumab prolongs overall survival (OS) over that achieved with docetaxel among patients with previously treated non-small cell lung cancer.
Atezolizumab prolongs overall survival (OS) over that achieved with docetaxel among patients with previously treated non-small cell lung cancer (NSCLC), and improvement was associated with programmed death ligand 1 (PD-L1) expression on tumor cells and tumor-infiltrating immune cells, according to a report from the open-label phase II randomized controlled POPLAR trialpublished in The Lancet.
“These data, along with those from other atezolizumab studies in patients with previously treated NSCLC, demonstrate the clinical efficacy and safety of targeting PD-L1 with atezolizumab in this patient population,” the coauthors concluded.
A total of 142 patients were administered atezolizumab (1200 mg) and 135 patients were administered docetaxel (75 mg/m2) once every 3 weeks. OS in the intention-to-treat population was 12.6 months for atezolizumab versus 9.7 months for docetaxel (hazard ratio [HR] 0.73; 95% CI: 0.53-0.99; P = .04).
The findings also suggested that PD-L1 expression may predict atezolizumab benefit. “In our exploratory analysis, patients with pre-existing immunity, defined by high T-effector-interferon-Î³-associated gene expression, had improved overall survival with atezolizumab,” the coauthors reported.
Overall, atezolizumab was well-tolerated with lower rates of drug discontinuation compared to docetaxel; 11 (8%) patients in the atezolizumab group discontinued because of adverse events versus 30 (22%) patients in the docetaxel group. Potential immune-mediated adverse events, such as increased aspartate aminotransferase, increased alanine aminotransferase, pneumonitis, colitis, and hepatitis occurred at low frequencies (<5%) in the atezolizumab group and were generally manageable and reversible.
“A key strength of POPLAR was that this study enrolled patients irrespective of PD-L1 status, which was prospectively assessed on both tumor cells and tumor-infiltrating immune cells,” the authors reported.
“The exploratory analyses of T-effector and interferon Î³ gene signature deepens our understanding of mechanisms of response to anti-PD-L1 blockade and provides a starting point for development of future predictive biomarkers for cancer immunotherapies,” they wrote.
The relatively small number of patients enrolled in the study diminished opportunities for robust subgroup analyses.