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Safety and clinical activity of atezolizumab monotherapy in metastatic non-small-cell lung cancer: final results from a phase I study.
- Source :
-
European Journal of Cancer . Sep2018, Vol. 101, p201-209. 9p. - Publication Year :
- 2018
-
Abstract
- Introduction 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. Methods 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. Results 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. Conclusions 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. ClinicalTrials.gov identifier NCT01375842 . [ABSTRACT FROM AUTHOR]
- Subjects :
- *ATEZOLIZUMAB
*THERAPEUTIC use of monoclonal antibodies
*LUNG cancer prognosis
*HYPOXEMIA
*APPETITE
*CELL lines
*CLINICAL trials
*CONFIDENCE intervals
*DYSPNEA
*FATIGUE (Physiology)
*GENE expression
*HYPONATREMIA
*IMMUNOHISTOCHEMISTRY
*INTRAVENOUS therapy
*LONGITUDINAL method
*LUNG cancer
*METASTASIS
*MONOCLONAL antibodies
*GENETIC mutation
*NAUSEA
*PNEUMONIA
*RESEARCH
*SURVIVAL
*TUMOR grading
*PROGNOSIS
Subjects
Details
- Language :
- English
- ISSN :
- 09598049
- Volume :
- 101
- Database :
- Academic Search Index
- Journal :
- European Journal of Cancer
- Publication Type :
- Academic Journal
- Accession number :
- 131316579
- Full Text :
- https://doi.org/10.1016/j.ejca.2018.06.031