Safety and clinical activity of atezolizumab monotherapy in metastatic non-small-cell lung cancer: final results from a phase I study

Atezolizumab, an anti-programmed death-ligand 1 (PD-L1) antibody, inhibits PD-L1:PD-1 and PD-L1:B7.1 interactions, restoring anticancer immunity. Here, we report final analyses from the non-small-cell lung cancer (NSCLC) cohort of the first atezolizumab phase I study. Patients with NSCLC received atezolizumab 1–20 mg/kg or 1200 mg intravenously every 3 weeks. Baseline PD-L1 expression on tumour cells (TCs) and tumour-infiltrating immune cells (ICs) was assessed (VENTANA SP142 immunohistochemistry assay). Exploratory subgroup analyses investigated responses by baseline PD-L1 expression and oncogenic mutational status. Eighty-nine patients, 98% of whom had received previous systemic therapy, were evaluable for safety and antitumour activity. Atezolizumab was well tolerated, with grade III/IV treatment-related adverse events (TRAEs) observed in 10 patients (11%). All-grade TRAEs occurring in >10% of patients were fatigue, nausea and decreased appetite; grade III/IV TRAEs occurring in >2% of patients were fatigue, dyspnoea, hyponatremia and hypoxia. One patient died from treatment-unrelated pneumonia. Objective response rate (ORR) was 50% (95% confidence interval [CI], 28%–72%), 33% (20%–48%), 29% (18%–41%) and 11% (1%–35%) for the TC3 or IC3, TC2/3 or IC2/3, TC1/2/3 or IC1/2/3 and TC0 and IC0 subgroups, respectively. All-patient ORR was 23% (95% CI, 14%–33%). Median duration of response was 16.4 months (range, 7.2–53.4+). One-, 2-, and 3-year survival rates were 63% (95% CI, 53%–73%), 37% (26%–47%) and 28% (18%–38%), respectively. Single-agent atezolizumab was well tolerated with long-term clinical benefits, including durable responses and survival, in pretreated NSCLC. Improved responses and survival rates were seen with increasing baseline PD-L1 expression. NCT01375842. •Five-year follow-up of patients with NSCLC receiving single-agent atezolizumab.•Atezolizumab continued to be well tolerated with a favourable safety profile.•Responses with atezolizumab were durable with sustained survival benefit.•PD-L1 expression enriches for clinical benefit with atezolizumab.•Patients with no-to-low PD-L1 tumour expression derive benefit with atezolizumab.