Strategies to overcome acquired resistance to EGFR TKI in the treatment of non-small cell lung cancer

TargetingHER2Aberrations in Non–Small Cell Lung Cancer with Osimertinib

(2018) Shengwu Liu et al.   CLINICAL CANCER RESEARCH

First-in-Human Phase I Study of AC0010, a Mutant-Selective EGFR Inhibitor in Non–Small Cell Lung Cancer: Safety, Efficacy, and Potential Mechanism of Resistance

(2018) Yuxiang Ma et al.   Journal of Thoracic Oncology

Nivolumab Plus Erlotinib in Patients With EGFR -Mutant Advanced NSCLC

(2018) Scott Gettinger et al.   Journal of Thoracic Oncology

Durvalumab as third-line or later treatment for advanced non-small-cell lung cancer (ATLANTIC): an open-label, single-arm, phase 2 study

(2018) Marina Chiara Garassino et al.   LANCET ONCOLOGY

Atezolizumab for First-Line Treatment of Metastatic Nonsquamous NSCLC

(2018) Mark A. Socinski et al.   NEW ENGLAND JOURNAL OF MEDICINE

Osimertinib in Untreated EGFR-Mutated Advanced Non–Small-Cell Lung Cancer

(2018) Jean-Charles Soria et al.   NEW ENGLAND JOURNAL OF MEDICINE

Epigenetic silencing of miR-483-3p promotes acquired gefitinib resistance and EMT in EGFR-mutant NSCLC by targeting integrin β3

(2018) Jinnan Yue et al.   ONCOGENE

Feasibility of re-biopsy and EGFR mutation analysis in patients with non-small cell lung cancer

(2018) Tae-Ok Kim et al.   Thoracic Cancer

Combined inhibition of MEK and PI3K pathways overcomes acquired resistance to EGFR-TKIs in non-small cell lung cancer

(2018) Hiroki Sato et al.   CANCER SCIENCE

Phase Ib/II Study of Capmatinib (INC280) Plus Gefitinib After Failure of Epidermal Growth Factor Receptor (EGFR) Inhibitor Therapy in Patients With EGFR-Mutated, MET Factor–Dysregulated Non–Small-Cell Lung Cancer

(2018) Yi-Long Wu et al.   JOURNAL OF CLINICAL ONCOLOGY

Epithelial-mesenchymal transition (EMT) beyond EGFR mutations per se is a common mechanism for acquired resistance to EGFR TKI

(2018) Chien-Hui Weng et al.   ONCOGENE

Epithelial-to-mesenchymal transition (EMT) causing acquired resistance to afatinib in a patient with epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma

(2018) Mau-Ern Poh et al.   Journal of Thoracic Disease

Assessment of Resistance Mechanisms and Clinical Implications in Patients With EGFR T790M–Positive Lung Cancer and Acquired Resistance to Osimertinib

(2018) Geoffrey R. Oxnard et al.   JAMA Oncology

Assessment of the Mutational Status of NSCLC Using Hypermetabolic Circulating Tumor Cells

(2018) Matteo Turetta et al.   Cancers

Activation of AXL as a Preclinical Acquired Resistance Mechanism Against Osimertinib Treatment in EGFR-Mutant Non–Small Cell Lung Cancer Cells

(2018) Kei Namba et al.   MOLECULAR CANCER RESEARCH

AXL–GAS6 expression can predict for adverse prognosis in non-small cell lung cancer with brain metastases

(2017) Xiaoliang Wu et al.   JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY

Osimertinib in Pretreated T790M-Positive Advanced Non–Small-Cell Lung Cancer: AURA Study Phase II Extension Component

(2017) James Chih-Hsin Yang et al.   JOURNAL OF CLINICAL ONCOLOGY

Gefitinib Plus Chemotherapy Versus Chemotherapy in Epidermal Growth Factor Receptor Mutation–Positive Non–Small-Cell Lung Cancer Resistant to First-Line Gefitinib (IMPRESS): Overall Survival and Biomarker Analyses

(2017) Tony S.K. Mok et al.   JOURNAL OF CLINICAL ONCOLOGY

Non–Small Cell Lung Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology

(2017) David S. Ettinger et al.   Journal of the National Comprehensive Cancer Network

P3.02b-001 Phase 1 Dose Escalation of PF-06747775 (EGFR-T790M Inhibitor) in Patients with Advanced EGFRm (Del 19 or L858R+/-T790M) NSCLC

(2017) Hatim Husain et al.   Journal of Thoracic Oncology

Capture-Based Targeted Ultradeep Sequencing in Paired Tissue and Plasma Samples Demonstrates Differential Subclonal ctDNA-Releasing Capability in Advanced Lung Cancer

(2017) Xiaowei Mao et al.   Journal of Thoracic Oncology

Acquired BRAF V600E Mutation as Resistant Mechanism after Treatment with Osimertinib

(2017) Chao-Chi Ho et al.   Journal of Thoracic Oncology

Checkpoint Inhibitors in Metastatic EGFR- Mutated Non–Small Cell Lung Cancer—A Meta-Analysis

(2017) Chee Khoon Lee et al.   Journal of Thoracic Oncology

Plasma ctDNA Analysis for Detection of the EGFR  T790M Mutation in Patients with Advanced Non–Small Cell Lung Cancer

(2017) Suzanne Jenkins et al.   Journal of Thoracic Oncology

Dacomitinib versus gefitinib as first-line treatment for patients with EGFR -mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial

(2017) Yi-Long Wu et al.   LANCET ONCOLOGY

EGFR T790M mutation testing within the osimertinib AURA Phase I study

(2017) Simon Dearden et al.   LUNG CANCER

Distinct Afatinib Resistance Mechanisms Identified in Lung Adenocarcinoma Harboring an EGFR Mutation

(2017) Toshimitsu Yamaoka et al.   MOLECULAR CANCER RESEARCH

Osimertinib or Platinum–Pemetrexed in EGFR T790M–Positive Lung Cancer

(2017) Tony S. Mok et al.   NEW ENGLAND JOURNAL OF MEDICINE

Targeting the miR-200c/LIN28B axis in acquired EGFR-TKI resistance non-small cell lung cancer cells harboring EMT features

(2017) Hiroki Sato et al.   Scientific Reports

Cross-Platform Comparison of Four Leading Technologies for Detecting EGFR Mutations in Circulating Tumor DNA from Non-Small Cell Lung Carcinoma Patient Plasma

(2017) Ting Xu et al.   Theranostics

Continuation of gefitinib plus chemotherapy prolongs progression-free survival in advanced non-small cell lung cancer patients who get acquired resistance to gefitinib without T790M mutations

(2017) Ting Ding et al.   Journal of Thoracic Disease

The Surveillance, Epidemiology, and End Results (SEER) Program and Pathology

(2016) Máire A. Duggan et al.   AMERICAN JOURNAL OF SURGICAL PATHOLOGY

Detection of ubiquitous and heterogeneous mutations in cell-free DNA from patients with early-stage non-small-cell lung cancer

(2016) M. Jamal-Hanjani et al.   ANNALS OF ONCOLOGY

Mutational status of synchronous and metachronous tumor samples in patients with metastatic non-small-cell lung cancer

(2016) Gilles Quéré et al.   BMC CANCER

EGF816 Exerts Anticancer Effects in Non–Small Cell Lung Cancer by Irreversibly and Selectively Targeting Primary and Acquired Activating Mutations in the EGF Receptor

(2016) Yong Jia et al.   CANCER RESEARCH

Rebiopsy for patients with non-small-cell lung cancer after epidermal growth factor receptor-tyrosine kinase inhibitor failure

(2016) Takahisa Kawamura et al.   CANCER SCIENCE

Association Between Plasma Genotyping and Outcomes of Treatment With Osimertinib (AZD9291) in Advanced Non–Small-Cell Lung Cancer

(2016) Geoffrey R. Oxnard et al.   JOURNAL OF CLINICAL ONCOLOGY

NCCN Guidelines Insights: Non–Small Cell Lung Cancer, Version 4.2016

(2016) David S. Ettinger et al.   Journal of the National Comprehensive Cancer Network

Acquired Resistance to First-Line Afatinib and the Challenges of Prearranged Progression Biopsies

(2016) Meghan Campo et al.   Journal of Thoracic Oncology

HER2 Amplification and HER2 Mutation Are Distinct Molecular Targets in Lung Cancers

(2016) Bob T. Li et al.   Journal of Thoracic Oncology

1300: Efficacy and safety of BI 1482694 (HM61713), an EGFR mutant-specific inhibitor, in T790M-positive NSCLC at the recommended phase II dose

(2016) K. Park et al.   Journal of Thoracic Oncology

Osimertinib for pretreated EGFR Thr790Met-positive advanced non-small-cell lung cancer (AURA2): a multicentre, open-label, single-arm, phase 2 study

(2016) Glenwood Goss et al.   LANCET ONCOLOGY

Overcoming EGFR(T790M) and EGFR(C797S) resistance with mutant-selective allosteric inhibitors

(2016) Yong Jia et al.   NATURE

Anexelekto (AXL) Increases Resistance to EGFR-TKI and Activation of AKT and ERK1/2 in Non-Small Cell Lung Cancer Cells

(2016) Yaqiong Tian et al.   ONCOLOGY RESEARCH

Circulating tumor DNA detection in lung cancer patients before and after surgery

(2016) Nannan Guo et al.   Scientific Reports

Association of EGFR Exon 19 Deletion and EGFR-TKI Treatment Duration with Frequency of T790M Mutation in EGFR-Mutant Lung Cancer Patients

(2016) Norikazu Matsuo et al.   Scientific Reports

The Allelic Context of the C797S Mutation Acquired upon Treatment with Third-Generation EGFR Inhibitors Impacts Sensitivity to Subsequent Treatment Strategies

(2015) M. J. Niederst et al.   CLINICAL CANCER RESEARCH

Spatiotemporal T790M Heterogeneity in Individual Patients with EGFR-Mutant Non–Small-Cell Lung Cancer after Acquired Resistance to EGFR-TKI

(2015) Akito Hata et al.   Journal of Thoracic Oncology

Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials

(2015) James Chih-Hsin Yang et al.   LANCET ONCOLOGY

Gefitinib plus chemotherapy versus placebo plus chemotherapy in EGFR-mutation-positive non-small-cell lung cancer after progression on first-line gefitinib (IMPRESS): a phase 3 randomised trial

(2015) Jean-Charles Soria et al.   LANCET ONCOLOGY

EGFR mutation detection in ctDNA from NSCLC patient plasma: A cross-platform comparison of leading technologies to support the clinical development of AZD9291

(2015) Kenneth S. Thress et al.   LUNG CANCER

EGFR inhibitor and chemotherapy combinations for acquired TKI resistance in EGFR-mutant NSCLC models

(2015) Niina Laurila et al.   MEDICAL ONCOLOGY

Inhibition of IGF1R signaling abrogates resistance to afatinib (BIBW2992) in EGFR T790M mutant lung cancer cells

(2015) Yongik Lee et al.   MOLECULAR CARCINOGENESIS

Rociletinib in EGFR-Mutated Non–Small-Cell Lung Cancer

(2015) Lecia V. Sequist et al.   NEW ENGLAND JOURNAL OF MEDICINE

AZD9291 in EGFR Inhibitor–Resistant Non–Small-Cell Lung Cancer

(2015) Pasi A. Jänne et al.   NEW ENGLAND JOURNAL OF MEDICINE

Randomized Phase II Trial of Erlotinib Beyond Progression in Advanced Erlotinib-Responsive Non-Small Cell Lung Cancer

(2015) B. Halmos et al.   ONCOLOGIST

Impact of Continuing First-Line EGFR Tyrosine Kinase Inhibitor Therapy Beyond RECIST Disease Progression in Patients with Advanced EGFR-Mutated Non-Small-Cell Lung Cancer (NSCLC): Retrospective GFPC 04-13 Study

(2015) J. B. Auliac et al.   Targeted Oncology

Association of PD-L1 overexpression with activating EGFR mutations in surgically resected nonsmall-cell lung cancer

(2014) K. Azuma et al.   ANNALS OF ONCOLOGY

A peptide antigen derived from EGFR T790M is immunogenic in non-small cell lung cancer

(2014) KAZUYA OFUJI et al.   INTERNATIONAL JOURNAL OF ONCOLOGY

A Prospective, Molecular Epidemiology Study of EGFR Mutations in Asian Patients with Advanced Non–Small-Cell Lung Cancer of Adenocarcinoma Histology (PIONEER)

(2014) Yuankai Shi et al.   Journal of Thoracic Oncology

Combined gefitinib and pemetrexed overcome the acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer

(2014) MIN WU et al.   Molecular Medicine Reports

Antitumor activity of combination treatment with gefitinib and docetaxel in EGFR-TKI-sensitive, primary resistant and acquired resistant human non-small cell lung cancer cells

(2014) MIN WU et al.   Molecular Medicine Reports

PIK3CA Mutations Frequently Coexist with EGFR/KRAS Mutations in Non-Small Cell Lung Cancer and Suggest Poor Prognosis in EGFR/KRAS Wildtype Subgroup

(2014) Lei Wang et al.   PLoS One

AZD9291, an Irreversible EGFR TKI, Overcomes T790M-Mediated Resistance to EGFR Inhibitors in Lung Cancer

(2014) D. A. E. Cross et al.   Cancer Discovery

Dual Inhibition of EGFR with Afatinib and Cetuximab in Kinase Inhibitor-Resistant EGFR-Mutant Lung Cancer with and without T790M Mutations

(2014) Y. Y. Janjigian et al.   Cancer Discovery

MET and AXL Inhibitor NPS-1034 Exerts Efficacy against Lung Cancer Cells Resistant to EGFR Kinase Inhibitors Because of MET or AXL Activation

(2013) J. K. Rho et al.   CANCER RESEARCH

Analysis of Tumor Specimens at the Time of Acquired Resistance to EGFR-TKI Therapy in 155 Patients with EGFR-Mutant Lung Cancers

(2013) H. A. Yu et al.   CLINICAL CANCER RESEARCH

Acquired Resistance to Targeted Therapies Against Oncogene-Driven Non–Small-Cell Lung Cancer: Approach to Subtyping Progressive Disease and Clinical Implications

(2013) David R. Gandara et al.   Clinical Lung Cancer

PARAMOUNT: Final Overall Survival Results of the Phase III Study of Maintenance Pemetrexed Versus Placebo Immediately After Induction Treatment With Pemetrexed Plus Cisplatin for Advanced Nonsquamous Non–Small-Cell Lung Cancer

(2013) Luis G. Paz-Ares et al.   JOURNAL OF CLINICAL ONCOLOGY

Randomized Phase II Trial of Onartuzumab in Combination With Erlotinib in Patients With Advanced Non–Small-Cell Lung Cancer

(2013) David R. Spigel et al.   JOURNAL OF CLINICAL ONCOLOGY

Phase III Study of Afatinib or Cisplatin Plus Pemetrexed in Patients With Metastatic Lung Adenocarcinoma WithEGFRMutations

(2013) Lecia V. Sequist et al.   JOURNAL OF CLINICAL ONCOLOGY

EGFR tyrosine kinase inhibitors beyond focal progression obtain a prolonged disease control in patients with advanced adenocarcinoma of the lung

(2013) Fabio Conforti et al.   LUNG CANCER

Rapid increase of serum neuron specific enolase level and tachyphylaxis of EGFR-tyrosine kinase inhibitor indicate small cell lung cancer transformation from EGFR positive lung adenocarcinoma?

(2013) Yan Zhang et al.   LUNG CANCER

Clinical characteristics of non-small cell lung cancer patients who experienced acquired resistance during gefitinib treatment

(2013) Hye-Ryoun Kim et al.   LUNG CANCER

Chemotherapy With Erlotinib or Chemotherapy Alone in Advanced Non-Small Cell Lung Cancer With Acquired Resistance to EGFR Tyrosine Kinase Inhibitors

(2013) S. B. Goldberg et al.   ONCOLOGIST

Discovery of a Mutant-Selective Covalent Inhibitor of EGFR that Overcomes T790M-Mediated Resistance in NSCLC

(2013) A. O. Walter et al.   Cancer Discovery

Activation of the PD-1 Pathway Contributes to Immune Escape in EGFR-Driven Lung Tumors

(2013) E. A. Akbay et al.   Cancer Discovery

IGF-1R/epithelial-to-mesenchymal transition (EMT) crosstalk suppresses the erlotinib-sensitizing effect of EGFR exon 19 deletion mutations

(2013) Alejandro Vazquez-Martin et al.   Scientific Reports

Resistance to Irreversible EGF Receptor Tyrosine Kinase Inhibitors through a Multistep Mechanism Involving the IGF1R Pathway

(2012) A. B. Cortot et al.   CANCER RESEARCH

Combined EGFR/MET or EGFR/HSP90 Inhibition Is Effective in the Treatment of Lung Cancers Codriven by Mutant EGFR Containing T790M and MET

(2012) L. Xu et al.   CANCER RESEARCH

An Epithelial-Mesenchymal Transition Gene Signature Predicts Resistance to EGFR and PI3K Inhibitors and Identifies Axl as a Therapeutic Target for Overcoming EGFR Inhibitor Resistance

(2012) L. A. Byers et al.   CLINICAL CANCER RESEARCH

Efficacy of EGFR Tyrosine Kinase Inhibitors in Patients With EGFR-Mutated Non–Small-Cell Lung Cancer: A Meta-Analysis of 13 Randomized Trials

(2012) Fausto Petrelli et al.   Clinical Lung Cancer

Combined Erlotinib and Cetuximab overcome the acquired resistance to epidermal growth factor receptors tyrosine kinase inhibitor in non-small-cell lung cancer

(2012) Meng Wang et al.   JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY

Local Ablative Therapy of Oligoprogressive Disease Prolongs Disease Control by Tyrosine Kinase Inhibitors in Oncogene-Addicted Non–Small-Cell Lung Cancer

(2012) Andrew J. Weickhardt et al.   Journal of Thoracic Oncology

Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial

(2012) Rafael Rosell et al.   LANCET ONCOLOGY

Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer

(2012) Martin Peifer et al.   NATURE GENETICS

Activation of the AXL kinase causes resistance to EGFR-targeted therapy in lung cancer

(2012) Zhenfeng Zhang et al.   NATURE GENETICS

HER2 Amplification: A Potential Mechanism of Acquired Resistance to EGFR Inhibition in EGFR -Mutant Lung Cancers That Lack the Second-Site EGFR T790M Mutation

(2012) Ken Takezawa et al.   Cancer Discovery

Phase I/II Trial of Cetuximab and Erlotinib in Patients with Lung Adenocarcinoma and Acquired Resistance to Erlotinib

(2011) Y. Y. Janjigian et al.   CLINICAL CANCER RESEARCH

Disease Flare after Tyrosine Kinase Inhibitor Discontinuation in Patients with EGFR-Mutant Lung Cancer and Acquired Resistance to Erlotinib or Gefitinib: Implications for Clinical Trial Design

(2011) J. E. Chaft et al.   CLINICAL CANCER RESEARCH

Clinical Characteristics of Patients With Lung Adenocarcinomas HarboringBRAFMutations

(2011) Paul K. Paik et al.   JOURNAL OF CLINICAL ONCOLOGY

Phosphoinositide-3-Kinase Catalytic Alpha and KRAS Mutations are Important Predictors of Resistance to Therapy with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Patients with Advanced Non-small Cell Lung Cancer

(2011) Vienna Ludovini et al.   Journal of Thoracic Oncology

WZ4002, a third-generation EGFR inhibitor, can overcome anoikis resistance in EGFR-mutant lung adenocarcinomas more efficiently than Src inhibitors

(2011) Yuji Sakuma et al.   LABORATORY INVESTIGATION

Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study

(2011) Caicun Zhou et al.   LANCET ONCOLOGY

Continuous EGFR-TKI administration following radiotherapy for non-small cell lung cancer patients with isolated CNS failure

(2011) Takehito Shukuya et al.   LUNG CANCER

Treatment of Non–Small-Cell Lung Cancer with Erlotinib or Gefitinib

(2011) Vince D. Cataldo et al.   NEW ENGLAND JOURNAL OF MEDICINE

Genotypic and Histological Evolution of Lung Cancers Acquiring Resistance to EGFR Inhibitors

(2011) L. V. Sequist et al.   Science Translational Medicine

Acquired Resistance to EGFR Tyrosine Kinase Inhibitors in EGFR-Mutant Lung Cancer: Distinct Natural History of Patients with Tumors Harboring the T790M Mutation

(2010) Geoffrey R. Oxnard et al.   CLINICAL CANCER RESEARCH

Gefitinib or Chemotherapy for Non–Small-Cell Lung Cancer with Mutated EGFR

(2010) Makoto Maemondo et al.   NEW ENGLAND JOURNAL OF MEDICINE

Crosstalk Between Epidermal Growth Factor Receptor- and Insulin-Like Growth Factor-1 Receptor Signaling: Implications for Cancer Therapy

(2009) J. Veeken et al.   CURRENT CANCER DRUG TARGETS

Clinical Definition of Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non–Small-Cell Lung Cancer

(2009) David Jackman et al.   JOURNAL OF CLINICAL ONCOLOGY

Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non-small-cell lung cancer: a randomised, double-blind, phase 3 study

(2009) Tudor Ciuleanu et al.   LANCET

Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial

(2009) Tetsuya Mitsudomi et al.   LANCET ONCOLOGY

Screening for Epidermal Growth Factor Receptor Mutations in Lung Cancer

(2009) Rafael Rosell et al.   NEW ENGLAND JOURNAL OF MEDICINE

MET increased gene copy number and primary resistance to gefitinib therapy in non-small-cell lung cancer patients

(2008) F. Cappuzzo et al.   ANNALS OF ONCOLOGY

BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models

(2008) D Li et al.   ONCOGENE