FIR: Efficacy, Safety, and Biomarker Analysis of a Phase II Open-Label Study of Atezolizumab in PD-L1-Selected Patients With NSCLC.

Abstract

INTRODUCTION:

The FIR phase II study (NCT01846416) evaluated the efficacy and safety of anti-programmed death-ligand 1 (PD-L1) atezolizumab in advanced NSCLC selected by tumor cell (TC) or tumor-infiltrating immune cell (IC) PD-L1 expression.

METHODS:

Patients with PD-L1 TC2/3 (PD-L1 staining on ≥5% of TC) or IC2/3 tumors (PD-L1 staining on ≥5% of IC; determined by SP142 PD-L1 immunohistochemistry assay) with paired fresh and archival histology samples were recruited into cohort 1 (chemotherapy-naive/>6 months between adjuvant chemotherapy and recurrence), cohort 2 (≥ second-line without brain metastases), or cohort 3 (≥ second-line with treated brain metastases). Patients received 1200 mg atezolizumab on day 1 (21-day cycles). Primary endpoint was investigator-assessed modified Response Evaluation Criteria in Solid Tumors, objective response rate (Response Evaluation Criteria in Solid Tumors v1.1). Secondary endpoints were overall survival, progression-free survival, duration of response, and safety.

RESULTS:

Patients (N = 138) were enrolled (137 evaluable for response: cohort 1, n = 31; cohort 2, n = 93; and cohort 3, n = 13). Investigator-assessed objective response rate was 32%, 21%, and 23% for cohorts 1, 2, and 3, respectively. Treatment-related adverse events were reported in 81%, 67%, and 69% of patients, respectively, including grade 3-4 treatment-related adverse events in 16%, 19%, and 15%, respectively. Moreover, 88.6% (86 of 97) paired baseline tumor samples had <5% change in TC/IC PD-L1 expression over time.

CONCLUSIONS:

Atezolizumab monotherapy showed clinical activity in patients with NSCLC, including those with brain metastases; safety was consistent with previous trials. Atezolizumab has completed phase III monotherapy studies in second-line. Front-line trials are ongoing, confirming these favorable results.

• Authors: David R Spigel, Jamie E Chaft, Scott Gettinger, Bo H Chao, Luc Dirix, Peter Schmid, Laura Q M Chow, Rodney J Hicks, Larry Leon, Jill Fredrickson, Marcin Kowanetz, Alan Sandler, Roel Funke, Naiyer A Rizvi
• Journal: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer (J Thorac Oncol) Vol. 13 Issue 11 Pg. 1733-1742 (11 2018) ISSN: 1556-1380 [Electronic] United States
• PMID: 29775807 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents
• B7-H1 Antigen
• CD274 protein, human
• atezolizumab

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal (therapeutic use)
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents (therapeutic use)
• B7-H1 Antigen (genetics)
• Carcinoma, Non-Small-Cell Lung (drug therapy, pathology)
• Female
• Humans
• Immunotherapy (methods)
• Lung Neoplasms (drug therapy, pathology)
• Male
• Middle Aged