@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: National Institutes of Health/National Cancer InstituteNIHNCIP50CA196530P01CA129243R01CA195720R01CA208403F32CA210516Italian Association for Cancer ResearchDepartment of Defense Lung Cancer Research Program IdeaW81XWH-17-1-0351Diane and David Heller FoundationGinny and Kenneth Grunley Fund for Lung Cancer ResearchBrown Performance Group Fund for Innovation in Cancer InformaticsDruckenmiller Center for Lung Cancer ResearchNCIP30CA016359P30CA008748Damon Runyon Clinical InvestigatorDamon Runyon Cancer Research FoundationCI-98-18Parker Institute for Cancer ImmunotherapyYale Cancer Center 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: HAY is a consultant for AstraZeneca and has received travel support from Eli Lilly. Her institution, Memorial Sloan Kettering has received research funding from Astellas Pharma, AstraZeneca, Daiichi, Eli Lilly, Novartis, and Pfizer for clinical trials she is involved in. She is listed as an inventor on a patent application submitted for pulsatile use of erlotinib to treat or prevent brain metastases. AL receives research support (to UCLA) from Daiichi, Calithera, Dracen, and AstraZeneca; is on the advisory board for AstraZeneca and Bristol–Myers Squibb; is also a consultant for Leica Biosystems and his wife is an employee of and owns stock from Boston Scientific. AT is currently an employee of MSD, however, these studies were conducted when she was at Yale. BSH is a consultant for Boehringer Ingelheim and previously owned stock in Abbvie. GJR receives collaborative research funding (to MSKCC) from Novartis, Roche, Pfizer, Mirati, Merck, and Takeda; has consulted for Merck and Roche; and has received travel support from Merck. MEA has received speaker and consulting fees from Invivoscribe and Biocartis. ML receives research support from LOXO Oncology and Helsinn Therapeutics, and he is an ad hoc advisory board member at AstraZeneca, Bristol-Myers Squibb, Merck, Takeda, and Bayer. RSH receives research support from AstraZeneca, Eli Lilly and Company, and Merck and Company; is a paid consultant to Abbvie Pharmaceuticals, ARMO Biosciences, AstraZeneca, Biodesix, Bristol-Myers Squibb, Eli Lilly and Company, EMD Serrano, Genentech/Roche, Genmab, Halozyme, Heat Biologics, Infinity Pharmaceuticals, Loxo Oncology, Merck and Company, Nektar, Neon Therapeutics, NextCure, Novartis, Pfizer, Sanofi, Seattle Genetics, Shire PLC, Spectrum Pharmaceuticals, Symphogen, Tocagen and Tesaro; is a scientific advisory board member at Neon Therapeutics, Infinity Pharmaceuticals, and NextCure; is a board member (non-executive/independent) at Junshi Pharmaceuticals. SBG receives research funding from AstraZeneca and research support (to Yale) from MedImmune, AstraZeneca, Spectrum, Genentech, Pfizer, Bristol–Myers Squibb, and Immunogen, and is a paid consultant for AstraZeneca, Boehringer Ingelheim, Bristol–Myers Squibb, Eli Lilly, Genentech, Amgen, and Spectrum. MMA has received research funding from Bristol-Myers Squibb, Eli Lilly, Genentech, and AstraZeneca, and he is a compensated consultant or has received honoraria from Abbvie, Ariad, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Merck, Genentech, Syndax, Nektar, Blueprint, and Maverick. JK is a consultant for Arterys. EBG has received research support (to UCLA) from AstraZeneca, Bristol-Myers Squibb, Genentech, Eli Lilly, Merck, Neon Pfizer, Dynavax, Iovance, Mirati, Novartis, and has received honoraria from Dracen. SG has received research support (to Yale) from Bristol-Myers Squibb, Genentech, Ariad/Takeda, Iovance, and is a consultant for Bristol-Myers Squibb and Nektar. MDH receives research funding from Bristol-Myers Squibb; is paid consultant to Merck, Bristol-Myers Squibb, AstraZeneca, Genentech/Roche, Janssen, Nektar, Syndax, Mirati, and Shattuck Labs; receives travel support/honoraria from AstraZeneca and Bristol-Myers Squibb; and a patent has been filed by MSK related to the use of tumor mutation burden to predict response to immunotherapy (PCT/US2015/062208), which has received licensing fees from PGDx. KP receives or has received research funding through her institution from AstraZeneca, Kolltan, Roche, Gilead, and Symphogen; consults or receives honoraria from Takeda, NCCN, Novartis, Merck, AstraZeneca, Tocagen, Maverick Therapeutics, and Dynamo Therapeutics; and is a co-inventor on a patent licensed to Molecular MD for EGFR T790M mutation testing (through MSKCC). All remaining authors have declared no conflicts of interest. 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",
}
