Third generation EGFR TKIs: current data and future directions

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

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

Discovery of N-((3R,4R)-4-Fluoro-1-(6-((3-methoxy-1-methyl-1H-pyrazol-4-yl)amino)-9-methyl-9H-purin-2-yl)pyrrolidine-3-yl)acrylamide (PF-06747775) through Structure-Based Drug Design: A High Affinity Irreversible Inhibitor Targeting Oncogenic EGFR Mutants with Selectivity over Wild-Type EGFR

(2017) Simon Planken et al.   JOURNAL OF MEDICINAL CHEMISTRY

Trisubstituted Pyridinylimidazoles as Potent Inhibitors of the Clinically Resistant L858R/T790M/C797S EGFR Mutant: Targeting of Both Hydrophobic Regions and the Phosphate Binding Site

(2017) Marcel Günther et al.   JOURNAL OF MEDICINAL CHEMISTRY

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

P3.02b-119 YH25448, a Highly Selective 3rd Generation EGFR TKI, Exhibits Superior Survival over Osimertinib in Animal Model with Brain Metastases from NSCLC

(2017) Min Hee Hong et al.   Journal of Thoracic Oncology

Lung Adenocarcinoma Harboring EGFR T790M and In Trans C797S Responds to Combination Therapy of First- and Third-Generation EGFR TKIs and Shifts Allelic Configuration at Resistance

(2017) Zhen Wang et al.   Journal of Thoracic Oncology

Novel Mutations on EGFR Leu792 Potentially Correlate to Acquired Resistance to Osimertinib in Advanced NSCLC

(2017) Kai Chen et al.   Journal of Thoracic Oncology

Successful Treatment with Gefitinib in Advanced Non–Small Cell Lung Cancer after Acquired Resistance to Osimertinib

(2017) Nuria Chic 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

MA16.11 CNS Response to Osimertinib in Patients with T790M-Positive Advanced NSCLC: Pooled Data from Two Phase II Trials

(2017) Glenwood Goss 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

Emergence of novel and dominant acquired EGFR solvent-front mutations at Gly796 (G796S/R) together with C797S/R and L792F/H mutations in one EGFR (L858R/T790M) NSCLC patient who progressed on osimertinib

(2017) Sai-Hong Ignatius Ou et al.   LUNG CANCER

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

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

Liquid biopsy genotyping in lung cancer: ready for clinical utility?

(2017) Wei-Lun Huang et al.   Oncotarget

Lung Cancer: EGFR Inhibitors with Low Nanomolar Activity against a Therapy-Resistant L858R/T790M/C797S Mutant

(2016) Marcel Günther et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Met gene amplification and protein hyperactivation is a mechanism of resistance to both first and third generation EGFR inhibitors in lung cancer treatment

(2016) Puyu Shi et al.   CANCER LETTERS

Preclinical Comparison of Osimertinib with Other EGFR-TKIs in EGFR-Mutant NSCLC Brain Metastases Models, and Early Evidence of Clinical Brain Metastases Activity

(2016) P. Ballard et al.   CLINICAL CANCER RESEARCH

Heterogeneous Mechanisms of Primary and Acquired Resistance to Third-Generation EGFR Inhibitors

(2016) S. Ortiz-Cuaran et al.   CLINICAL CANCER RESEARCH

Assessment of EGFR Mutation Status in Matched Plasma and Tumor Tissue of NSCLC Patients from a Phase I Study of Rociletinib (CO-1686)

(2016) C. Karlovich et al.   CLINICAL CANCER RESEARCH

Third-generation inhibitors targeting EGFR T790M mutation in advanced non-small cell lung cancer

(2016) Shuhang Wang et al.   Journal of Hematology & Oncology

Discovery of (R,E)-N-(7-Chloro-1-(1-[4-(dimethylamino)but-2-enoyl]azepan-3-yl)-1H-benzo[d]imidazol-2-yl)-2-methylisonicotinamide (EGF816), a Novel, Potent, and WT Sparing Covalent Inhibitor of Oncogenic (L858R, ex19del) and Resistant (T790M) EGFR Mutants for the Treatment of EGFR Mutant Non-Small-Cell Lung Cancers

(2016) Gérald Lelais et al.   JOURNAL OF MEDICINAL CHEMISTRY

A Novel EGFR C797 Variant Detected in a Pleural Biopsy Specimen from an Osimertinib-Treated Patient Using a Comprehensive Hybrid Capture–Based Next-Generation Sequencing Assay

(2016) Roopika Menon et al.   Journal of Thoracic Oncology

Two Cases of Small Cell Lung Cancer Transformation from EGFR Mutant Adenocarcinoma During AZD9291 Treatment

(2016) Jun Soo Ham et al.   Journal of Thoracic Oncology

Acquired C797S Mutation upon Treatment with a T790M-Specific Third-Generation EGFR Inhibitor (HM61713) in Non–Small Cell Lung Cancer

(2016) Haa-Na Song et al.   Journal of Thoracic Oncology

L718Q Mutation as New Mechanism of Acquired Resistance to AZD9291 in EGFR -Mutated NSCLC

(2016) Melissa Bersanelli et al.   Journal of Thoracic Oncology

Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial

(2016) Keunchil Park et al.   LANCET 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

Next-generation epidermal growth factor receptor tyrosine kinase inhibitors in epidermal growth factor receptor -mutant non-small cell lung cancer

(2016) Chee-Seng Tan et al.   LUNG CANCER

High MET amplification level as a resistance mechanism to osimertinib (AZD9291) in a patient that symptomatically responded to crizotinib treatment post-osimertinib progression

(2016) Sai-Hong Ignatius Ou et al.   LUNG CANCER

AC0010, an Irreversible EGFR Inhibitor Selectively Targeting Mutated EGFR and Overcoming T790M-Induced Resistance in Animal Models and Lung Cancer Patients

(2016) X. Xu et al.   MOLECULAR CANCER THERAPEUTICS

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

(2016) Yong Jia et al.   NATURE

Update to Rociletinib Data with the RECIST Confirmed Response Rate

(2016) Lecia V. Sequist et al.   NEW ENGLAND JOURNAL OF MEDICINE

Inhibition of oxidative phosphorylation suppresses the development of osimertinib resistance in a preclinical model of EGFR-driven lung adenocarcinoma

(2016) Matthew J. Martin et al.   Oncotarget

EGFR-independent mechanisms of acquired resistance to AZD9291 in EGFR T790M-positive NSCLC patients

(2015) D. Planchard et al.   ANNALS OF ONCOLOGY

Acquired Resistance to the Mutant-Selective EGFR Inhibitor AZD9291 Is Associated with Increased Dependence on RAS Signaling in Preclinical Models

(2015) C. A. Eberlein et al.   CANCER RESEARCH

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

Detection of T790M, the Acquired Resistance EGFR Mutation, by Tumor Biopsy versus Noninvasive Blood-Based Analyses

(2015) T. K. Sundaresan et al.   CLINICAL CANCER RESEARCH

EGFR Mutations and Resistance to Irreversible Pyrimidine-Based EGFR Inhibitors

(2015) D. Ercan et al.   CLINICAL CANCER RESEARCH

Mechanisms of Acquired Resistance to AZD9291

(2015) Tae Min Kim et al.   Journal of Thoracic 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

Acquired EGFR C797S mutation mediates resistance to AZD9291 in non–small cell lung cancer harboring EGFR T790M

(2015) Kenneth S Thress et al.   NATURE MEDICINE

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

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

Heterogeneity Underlies the Emergence of EGFRT790 Wild-Type Clones Following Treatment of T790M-Positive Cancers with a Third-Generation EGFR Inhibitor

(2015) Z. Piotrowska et al.   Cancer Discovery

Liquid Biopsies: Genotyping Circulating Tumor DNA

(2014) Luis A. Diaz et al.   JOURNAL OF CLINICAL ONCOLOGY

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

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

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

Detection of Circulating Tumor Cells Harboring a Unique ALK Rearrangement in ALK-Positive Non–Small-Cell Lung Cancer

(2013) Emma Pailler et al.   JOURNAL OF CLINICAL ONCOLOGY

EGFR Array: Uses in the Detection of Plasma EGFR Mutations in Non–Small Cell Lung Cancer Patients

(2012) Irene Yam 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

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

Size-Selective Microcavity Array for Rapid and Efficient Detection of Circulating Tumor Cells

(2010) Masahito Hosokawa et al.   ANALYTICAL CHEMISTRY

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

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

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

Gefitinib or Carboplatin–Paclitaxel in Pulmonary Adenocarcinoma

(2009) Tony S. Mok et al.   NEW ENGLAND JOURNAL OF MEDICINE

Activating and resistance mutations of EGFR in non-small-cell lung cancer: role in clinical response to EGFR tyrosine kinase inhibitors

(2009) A F Gazdar   ONCOGENE