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Ann Oncol. 2019 May 14. pii: mdz141. doi: 10.1093/annonc/mdz141. [Epub ahead of print]

EGFR mutation subtypes and response to immune checkpoint blockade treatment in non-small cell lung cancer.

Author information

1
Yale Cancer Center, Yale University School of Medicine, New Haven, USA.
2
Department of Medicine, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, USA.
3
Weill Cornell Medical College, New York, USA.
4
Yale School of Public Health, New Haven, USA.
5
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering, New York, USA.
6
Marie-Josèe and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering, New York, USA.
7
Present Address: Department of Biostatistics and Data Management, Regeneron Pharmaceuticals, Tarrytown, USA.
8
Department of Genetics, Yale University School of Medicine, New Haven, USA.
9
Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, USA.
10
David Geffen School of Medicine, University of California Los Angeles, Los Angeles, USA.
11
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, USA.
12
Department of Pathology, Yale University School of Medicine, New Haven, USA.
13
Herbert Irving Comprehensive Cancer Center, Columbia University, New York, USA.
14
Department of Medicine, Columbia University Medical Center, New York, USA.
15
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, USA.
16
Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, USA.
17
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, USA.
18
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, USA.
19
Department of Medicine (Section of Medical Oncology), Yale University School of Medicine, New Haven, USA.

Abstract

BACKGROUND:

Although EGFR mutant tumors exhibit low response rates to immune checkpoint blockade overall, some EGFR mutant tumors do respond to these therapies. However, there is a lack of understanding of the characteristics of EGFR mutant lung tumors responsive to immune checkpoint blockade.

PATIENTS AND METHODS:

We retrospectivity analyzed de-identified clinical and molecular data on 171 cases of EGFR mutant lung tumors treated with immune checkpoint inhibitors from the Yale Cancer Center, Memorial Sloan Kettering Cancer Center, University of California Los Angeles, and Dana Farber Cancer Institute. A separate cohort of 383 EGFR mutant lung cancer cases with sequencing data available from the Yale Cancer Center, Memorial Sloan Kettering Cancer Center, and The Cancer Genome Atlas was compiled to assess the relationship between tumor mutation burden and specific EGFR alterations.

RESULTS:

Compared to 212 EGFR wild-type lung cancers, outcomes with PD-(L)1 blockade were worse in patients with lung tumors harboring alterations in exon 19 of EGFR (EGFRΔ19) but similar in EGFRL858R lung tumors. EGFRT790M status and PD-L1 expression did not impact response or survival outcomes to immune checkpoint blockade. PD-L1 expression was similar across EGFR alleles. Lung tumors with EGFRΔ19 alterations harbored a lower tumor mutation burden compared to EGFRL858R lung tumors despite similar smoking history.

CONCLUSIONS:

EGFR mutant tumors have generally low response to immune checkpoint inhibitors, but outcomes vary by allele. Understanding the heterogeneity of EGFR mutant tumors may be informative for establishing the benefits and uses of PD-(L)1 therapies for patients with this disease.

KEYWORDS:

Epidermal growth factor receptor; immune checkpoint blockade; non-small cell lung cancer

PMID:
31086949
DOI:
10.1093/annonc/mdz141

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