The PD-L1 inhibitor atezolizumab showed substantial responses as a single-agent treatment in patients with advanced non–small-cell lung cancer with confirmed PD-L1 expression.
The PD-L1 inhibitor atezolizumab showed substantial responses as a single-agent treatment in patients with advanced non-small-cell lung cancer (NSCLC) with confirmed PD-L1 expression, according to results of a new study.
“Patients with advanced NSCLC have only modest improvements in survival with systemic therapies,” wrote study authors led by Enriqueta Felip, MD, PhD, of Vall d'Hebron University Hospital in Barcelona, Spain. Immune checkpoint inhibitors have been shown to be effective in NSCLC; the new BIRCH trial was designed to assess atezolizumab’s activity across lines of therapy, using PD-L1 expression as a potential marker of response.
The phase II study included 659 patients with advanced NSCLC, no central nervous system metastases, and 0–2 prior lines of chemotherapy; all patients had confirmed PD-L1 expression. The study was divided into three cohorts: those treated with atezolizumab as first-line therapy (139 patients), a second-line group (268 patients), and a third-line or higher cohort (252 patients). Results of the study were published online ahead of print in the Journal of Clinical Oncology.
Patients had a median age of 64 years, and 59% were male. Most patients were current or previous tobacco users (64%), and most had non-squamous histology (72%).
The objective response rate (ORR) was 22% in first-line patients, 19% in second-line patients, and 18% in third-line or higher patients; complete responses were seen in 1%, 2%, and 2%, respectively. Patients with higher PD-L1 expression on tumor cells or tumor-infiltrating immune cells (accounting for 46% of the total study population) had an ORR of 31% with first-line atezolizumab, 26% with second-line therapy, and 27% with third-line or higher.
The median progression-free survival in the three cohorts was 5.4 months, 2.8 months, and 2.8 months, respectively. The median overall survival in the groups was 23.5 months, 15.5 months, and 13.2 months, respectively. First-line patients in the highest category of PD-L1 expression had a median OS of 26.9 months.
Almost all patients (94%) experienced at least one adverse event (AE), and 65% of those were treatment-related. Level of PD-L1 expression did not correlate with any change in the rate of AEs. The most common serious AEs included pneumonia (4%), dyspnea (3%), pyrexia (3%), and pneumonitis (2%). One case of treatment-related pneumonia was fatal.
“Data from BIRCH confirmed that single-agent atezolizumab provided clinical benefit in patients with advanced NSCLC,” the authors concluded. “Subgroup analyses conducted by varying PD-L1 levels support the hypothesis that atezolizumab treatment results in improvement in radiographic endpoints (eg, ORR) in patients with tumors that have the highest levels of PD-L1 expression.”