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Eur J Cancer. 2018 Sep;101:201-209. doi: 10.1016/j.ejca.2018.06.031. Epub 2018 Aug 1.

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

Author information

1
Vanderbilt-Ingram Cancer Center, Nashville, TN, USA. Electronic address: leora.horn@vanderbilt.edu.
2
Yale Comprehensive Cancer Center, Yale School of Medicine, New Haven, CT, USA.
3
HonorHealth Research Institute, Scottsdale, AZ, USA.
4
Dana-Farber Cancer Institute, Boston, MA, USA.
5
Vall D'Hebron University Hospital, Barcelona, Spain.
6
Massachusetts General Hospital Cancer Center, Boston, MA, USA.
7
Sarah Cannon Research Institute and Cancer Center, Tennessee Oncology, Nashville, TN, USA.
8
H. Lee Moffitt Cancer Center, Tampa, FL, USA.
9
The Angeles Clinic and Research Institute, Los Angeles, CA, USA.
10
Centre Léon-Bérard, Lyon, France.
11
Genentech, Inc., South San Francisco, CA, USA.
12
Gustave Roussy and University Paris-Sud, Villejuif, France.

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.

KEYWORDS:

Atezolizumab; Immune checkpoint inhibitor; Non-small-cell lung cancer; PD-L1

PMID:
30077125
DOI:
10.1016/j.ejca.2018.06.031
[Indexed for MEDLINE]

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