@article{b9eb42129848454f80596f7aa1c2f1f8,
title = "EGFR mutation subtypes and response to immune checkpoint blockade treatment in non-small-cell lung cancer",
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 retrospectively 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 with 212 EGFR wild-type lung cancers, outcomes with programmed cell death 1 or programmed death-ligand 1 (PD-(L)1) blockade were worse in patients with lung tumors harboring alterations in exon 19 of EGFR (EGFRΔ19) but similar for 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 with 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",
author = "K. Hastings and Yu, {H. A.} and W. Wei and F. Sanchez-Vega and M. Deveaux and J. Choi and H. Rizvi and A. Lisberg and A. Truini and Lydon, {C. A.} and Z. Liu and Henick, {B. S.} and A. Wurtz and G. Cai and Plodkowski, {A. J.} and Long, {N. M.} and Halpenny, {D. F.} and J. Killam and I. Oliva and N. Schultz and Riely, {G. J.} and Arcila, {M. E.} and M. Ladanyi and D. Zelterman and Herbst, {R. S.} and Goldberg, {S. B.} and Awad, {M. M.} and Garon, {E. B.} and S. Gettinger and Hellmann, {M. D.} and K. Politi",
note = "Funding Information: This work was supported by National Institutes of Health/National Cancer Institute (NIH/NCI) grants P50CA196530 (RSH, KP, SG, SBG, DZ), P01CA129243 (ML), R01CA195720 (KP), R01CA208403 (EBG), and F32CA210516 (KH), the Leslie H. Warner Fellowship to KH, the Italian Association for Cancer Research (AT), a Department of Defense Lung Cancer Research Program Idea Award W81XWH-17-1-0351 (KP), the Diane and David Heller Foundation, the Ginny and Kenneth Grunley Fund for Lung Cancer Research, the Brown Performance Group Fund for Innovation in Cancer Informatics (FSV), and the Druckenmiller Center for Lung Cancer Research at MSKCC. YCC and MSKCC shared resources used in this manuscript were in part supported by NIH/NCI Cancer Center Support Grants P30CA016359 and P30CA008748. MDH is a Damon Runyon Clinical Investigator supported in part by the Damon Runyon Cancer Research Foundation (CI-98-18) and is a member of the Parker Institute for Cancer Immunotherapy. Gilead Sciences, Inc. supported the sequencing of a subset of the Yale Cancer Center specimens. Funding Information: 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. epidermal growth factor receptor immune checkpoint blockade non-small-cell lung cancer National Institutes of Health/National Cancer Institute NIH 10.13039/100000002 NCI 10.13039/100000054 P50CA196530 P01CA129243 R01CA195720 R01CA208403 F32CA210516 Italian Association for Cancer Research 10.13039/501100005010 Department of Defense Lung Cancer Research Program Idea W81XWH-17-1-0351 Diane and David Heller Foundation Ginny and Kenneth Grunley Fund for Lung Cancer Research Brown Performance Group Fund for Innovation in Cancer Informatics Druckenmiller Center for Lung Cancer Research NIH 10.13039/100000002 NCI 10.13039/100000054 P30CA016359 P30CA008748 Damon Runyon Clinical Investigator Damon Runyon Cancer Research Foundation 10.13039/100001021 CI-98-18 Parker Institute for Cancer Immunotherapy Yale Cancer Center 10.13039/100010900 Publisher Copyright: {\textcopyright} 2019 The Author(s). Published by Oxford University Press on behalf of the European Society for Medical Oncology.",
year = "2019",
month = aug,
day = "1",
doi = "10.1093/annonc/mdz141",
language = "English",
volume = "30",
pages = "1311--1320",
journal = "Annals of Oncology",
issn = "0923-7534",
publisher = "Oxford University Press",
number = "8",
}