Biomarkers /
EGFR T790M
Overview
EGFR T790M is present in 0.53% of AACR GENIE cases, with lung adenocarcinoma, non-small cell lung carcinoma, unknown, squamous cell lung carcinoma, and conventional glioblastoma multiforme having the greatest prevalence [4].
Biomarker-Directed Therapies
EGFR T790M is a predictive biomarker for use of osimertinib, afatinib, dacomitinib, erlotinib, gefitinib, capmatinib, cetuximab, crizotinib, and pembrolizumab in patients.
Of the therapies with EGFR T790M as a predictive biomarker, 2 are FDA-approved and 8 have NCCN guidelines in at least one clinical setting.
Non-small cell lung carcinoma has the most therapies targeted against EGFR T790M or its related pathways [5].
Afatinib +
Non-Small Cell Lung Carcinoma -
Biomarker Criteria:
Sample must match all of the following:
Sample must match all of the following: Sample must match one or more of the following: |
Predicted Response: Acquired Resistance, Primary Resistance |
Clinical Setting(s): Metastatic (NCCN) | |
Note: EGFR T790M confers resistance to EGFR TKI therapy. |
Biomarker Criteria:
Sample must match all of the following:
|
Predicted Response: Primary Resistance |
Clinical Setting(s): Metastatic (NCCN) | |
Note: EGFR T790M confers resistance to EGFR TKI therapy. |
Dacomitinib +
Non-Small Cell Lung Carcinoma -
Biomarker Criteria:
Sample must match all of the following:
Sample must match all of the following: Sample must match one or more of the following: |
Predicted Response: Acquired Resistance, Primary Resistance |
Clinical Setting(s): Metastatic (NCCN) | |
Note: EGFR T790M confers resistance to EGFR TKI therapy. |
Biomarker Criteria:
Sample must match all of the following:
|
Predicted Response: Primary Resistance |
Clinical Setting(s): Metastatic (NCCN) | |
Note: EGFR T790M confers resistance to EGFR TKI therapy. |
Erlotinib +
Non-Small Cell Lung Carcinoma -
Biomarker Criteria:
Sample must match all of the following:
Sample must match all of the following: Sample must match one or more of the following: |
Predicted Response: Acquired Resistance, Primary Resistance |
Clinical Setting(s): Metastatic (NCCN) | |
Note: EGFR T790M confers resistance to EGFR TKI therapy. |
Biomarker Criteria:
Sample must match all of the following:
|
Predicted Response: Primary Resistance |
Clinical Setting(s): Metastatic (NCCN) | |
Note: EGFR T790M confers resistance to EGFR TKI therapy. |
Gefitinib +
Non-Small Cell Lung Carcinoma -
Biomarker Criteria:
Sample must match all of the following:
Sample must match all of the following: Sample must match one or more of the following: |
Predicted Response: Acquired Resistance, Primary Resistance |
Clinical Setting(s): Metastatic (NCCN) | |
Note: EGFR T790M confers resistance to EGFR TKI therapy. |
Biomarker Criteria:
Sample must match all of the following:
|
Predicted Response: Primary Resistance |
Clinical Setting(s): Metastatic (NCCN) | |
Note: EGFR T790M confers resistance to EGFR TKI therapy. |
Osimertinib +
Non-Small Cell Lung Carcinoma -
Biomarker Criteria:
Sample must match all of the following:
|
Predicted Response: Primary Sensitivity |
Clinical Setting(s): Metastatic (FDA, NCCN, ASCO) | |
Note: Indicated for metastatic, EGFR T790M mutation-positive non-small cell lung cancer (NSCLC) patients who have progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy. Also NCCN-recommended as adjuvant therapy. |
Biomarker Criteria:
Sample must match all of the following:
Sample must match one or more of the following: Sample must match one or more of the following: |
Predicted Response: Primary Resistance |
Clinical Setting(s): Metastatic (NCCN) | |
Note: According to NCCN, mutations in KRAS have been associated with reduced responsiveness to EGFR TKI therapy. |
Biomarker Criteria:
Sample must match all of the following:
|
Predicted Response: Acquired Resistance |
Clinical Setting(s): Metastatic (MCG) | |
Note: C797S mutation can be detected in ~40% of EGFR-mutant lung cancers that have developed acquired resistance to osimertinib. |
Biomarker Criteria:
Sample must match all of the following:
Sample must match one or more of the following: Sample must match all of the following: |
Predicted Response: Acquired Resistance |
Clinical Setting(s): Metastatic (MCG) | |
Note: C797S mutation can be detected in ~40% of EGFR-mutant lung cancers that have developed acquired resistance to osimertinib. |
Biomarker Criteria:
Sample must match all of the following:
|
Predicted Response: Primary Sensitivity |
Clinical Setting(s): Metastatic (NICE, SMC) | |
Note: Indicated for metastatic, EGFR T790M mutation-positive non-small cell lung cancer (NSCLC) patients who have progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy. |
Pembrolizumab +
Non-Small Cell Lung Carcinoma -
Biomarker Criteria:
Sample must match all of the following:
Sample must match one or more of the following: Sample must match one or more of the following: |
Predicted Response: Primary Sensitivity |
Clinical Setting(s): Metastatic (FDA) | |
Note: For PD-L1 expressing tumors (Tumor Proportion Score >=1%, clone 22C3) with an EGFR or ALK alteration: FDA-approved as subsequent line of therapy following targeted therapy. However, per NCCN, data in the second-line setting suggest that subsequent pembrolizumab monotherapy is less effective in tumors with an EGFR mutation or ALK rearrangement. |
Afatinib + Cetuximab +
Non-Small Cell Lung Carcinoma -
Biomarker Criteria:
Sample must match all of the following:
Sample must match one or more of the following: Sample must match one or more of the following: |
Predicted Response: Primary Sensitivity |
Clinical Setting(s): Metastatic (NCCN) | |
Note: Per NCCN, may be considered after progression on on afatinib, erlotinib, gefitinib, or dacomitinib, and chemotherapy. |
Capmatinib + Osimertinib +
Non-Small Cell Lung Carcinoma -
Biomarker Criteria:
Sample must match all of the following:
Sample must match one or more of the following: Sample must match one or more of the following: |
Predicted Response: Overcomes acquired resistance |
Clinical Setting(s): Metastatic (NCCN) | |
Note: To overcome resistance by secondary mutational events like MET amplification, EGFR must still be inhibited and additionally, a MET inhibitor must be added to the treatment. |
Crizotinib + Osimertinib +
Non-Small Cell Lung Carcinoma -
Biomarker Criteria:
Sample must match all of the following:
Sample must match all of the following: Sample must match one or more of the following: |
Predicted Response: Overcomes acquired resistance |
Clinical Setting(s): Metastatic (NCCN) | |
Note: To overcome resistance by secondary mutational events like MET amplification, EGFR must still be inhibited and additionally, a MET inhibitor must be added to the treatment. |
Clinical Trials
EGFR T790M serves as an inclusion eligibility criterion in 63 clinical trials, of which 44 are open and 19 are closed. Of the trials that contain EGFR T790M as an inclusion criterion, 1 is early phase 1 (1 open), 12 are phase 1 (8 open), 13 are phase 1/phase 2 (9 open), 30 are phase 2 (22 open), 4 are phase 3 (2 open), and 3 are no phase specified (2 open).
Trials with EGFR T790M in the inclusion eligibility criteria most commonly target non-small cell lung carcinoma, non-squamous non-small cell lung carcinoma, small cell lung carcinoma, lung adenocarcinoma, and lymphoma [5].
Osimertinib, pembrolizumab, pemetrexed, nivolumab, and carboplatin are the most frequent therapies in trials with EGFR T790M as an inclusion criteria [5].
Significance of EGFR T790M in Diseases
Non-Small Cell Lung Carcinoma +
EGFR is altered in 22.89% of non-small cell lung carcinoma patients with EGFR T790M present in 2.85% of all non-small cell lung carcinoma patients [4].
EGFR T790M is an inclusion criterion in 59 clinical trials for non-small cell lung carcinoma, of which 41 are open and 18 are closed. Of the trials that contain EGFR T790M and non-small cell lung carcinoma as inclusion criteria, 1 is early phase 1 (1 open), 11 are phase 1 (8 open), 13 are phase 1/phase 2 (9 open), 27 are phase 2 (19 open), 4 are phase 3 (2 open), and 3 are no phase specified (2 open) [5].
Osimertinib, afatinib, cetuximab, capmatinib, crizotinib, and pembrolizumab have evidence of efficacy in patients with EGFR T790M in non-small cell lung carcinoma [5].
Malignant Solid Tumor +
EGFR is altered in 7.61% of malignant solid tumor patients with EGFR T790M present in 0.5% of all malignant solid tumor patients [4].
EGFR T790M is an inclusion criterion in 5 clinical trials for malignant solid tumor, of which 4 are open and 1 is closed. Of the trials that contain EGFR T790M and malignant solid tumor as inclusion criteria, 1 is phase 1 (0 open), 2 are phase 1/phase 2 (2 open), and 2 are phase 2 (2 open) [5].
Lung Adenocarcinoma +
EGFR is altered in 26.09% of lung adenocarcinoma patients with EGFR T790M present in 3.4% of all lung adenocarcinoma patients [4].
EGFR T790M is an inclusion criterion in 2 clinical trials for lung adenocarcinoma, of which 2 are open and 0 are closed. Of the trials that contain EGFR T790M and lung adenocarcinoma as inclusion criteria, 2 are phase 2 (2 open) [5].
Squamous Cell Lung Carcinoma +
EGFR is altered in 6.88% of squamous cell lung carcinoma patients with EGFR T790M present in 0.3% of all squamous cell lung carcinoma patients [4].
EGFR T790M is an inclusion criterion in 2 clinical trials for squamous cell lung carcinoma, of which 2 are open and 0 are closed. Of the trials that contain EGFR T790M and squamous cell lung carcinoma as inclusion criteria, 2 are phase 2 (2 open) [5].
Colorectal Carcinoma +
EGFR is altered in 3.22% of colorectal carcinoma patients with EGFR T790M present in 0.01% of all colorectal carcinoma patients [4].
EGFR T790M is an inclusion criterion in 2 clinical trials for colorectal carcinoma, of which 1 is open and 1 is closed. Of the trials that contain EGFR T790M and colorectal carcinoma as inclusion criteria, 1 is phase 1 (0 open) and 1 is phase 2 (1 open) [5].
Non-Squamous Non-Small Cell Lung Carcinoma +
EGFR is altered in 25.27% of non-squamous non-small cell lung carcinoma patients with EGFR T790M present in 3.25% of all non-squamous non-small cell lung carcinoma patients [4].
EGFR T790M is an inclusion criterion in 1 clinical trial for non-squamous non-small cell lung carcinoma, of which 1 is open and 0 are closed. Of the trial that contains EGFR T790M and non-squamous non-small cell lung carcinoma as inclusion criteria, 1 is phase 2 (1 open) [5].
Lung Carcinoma +
EGFR is altered in 22.35% of lung carcinoma patients with EGFR T790M present in 2.74% of all lung carcinoma patients [4].
EGFR T790M is an inclusion criterion in 1 clinical trial for lung carcinoma, of which 1 is open and 0 are closed. Of the trial that contains EGFR T790M and lung carcinoma as inclusion criteria, 1 is phase 2 (1 open) [5].
Malignant Uterine Neoplasm +
EGFR is altered in 3.53% of malignant uterine neoplasm patients with EGFR T790M present in 0.03% of all malignant uterine neoplasm patients [4].
EGFR T790M is an inclusion criterion in 1 clinical trial for malignant uterine neoplasm, of which 1 is open and 0 are closed. Of the trial that contains EGFR T790M and malignant uterine neoplasm as inclusion criteria, 1 is phase 2 (1 open) [5].
Adenocarcinoma Of The Gastroesophageal Junction +
EGFR is altered in 5.0% of adenocarcinoma of the gastroesophageal junction patients [4].
EGFR T790M is an inclusion criterion in 1 clinical trial for adenocarcinoma of the gastroesophageal junction, of which 1 is open and 0 are closed. Of the trial that contains EGFR T790M and adenocarcinoma of the gastroesophageal junction as inclusion criteria, 1 is phase 2 (1 open) [5].
Bronchogenic Carcinoma +
EGFR T790M is an inclusion criterion in 1 clinical trial for bronchogenic carcinoma, of which 1 is open and 0 are closed. Of the trial that contains EGFR T790M and bronchogenic carcinoma as inclusion criteria, 1 is phase 2 (1 open) [5].
Esophageal Squamous Cell Carcinoma +
EGFR is altered in 8.16% of esophageal squamous cell carcinoma patients [4].
EGFR T790M is an inclusion criterion in 1 clinical trial for esophageal squamous cell carcinoma, of which 1 is open and 0 are closed. Of the trial that contains EGFR T790M and esophageal squamous cell carcinoma as inclusion criteria, 1 is phase 2 (1 open) [5].
Gastric Adenocarcinoma +
EGFR is altered in 5.93% of gastric adenocarcinoma patients [4].
EGFR T790M is an inclusion criterion in 1 clinical trial for gastric adenocarcinoma, of which 1 is open and 0 are closed. Of the trial that contains EGFR T790M and gastric adenocarcinoma as inclusion criteria, 1 is phase 2 (1 open) [5].
Head And Neck Carcinoma +
EGFR is altered in 4.29% of head and neck carcinoma patients [4].
EGFR T790M is an inclusion criterion in 1 clinical trial for head and neck carcinoma, of which 1 is open and 0 are closed. Of the trial that contains EGFR T790M and head and neck carcinoma as inclusion criteria, 1 is phase 2 (1 open) [5].
Small Cell Lung Carcinoma +
EGFR is altered in 9.38% of small cell lung carcinoma patients [4].
EGFR T790M is an inclusion criterion in 1 clinical trial for small cell lung carcinoma, of which 1 is open and 0 are closed. Of the trial that contains EGFR T790M and small cell lung carcinoma as inclusion criteria, 1 is phase 1 (1 open) [5].
References
1. Hart R and Prlic A. Universal Transcript Archive Repository. Version uta_20180821. San Francisco CA: Github;2015. https://github.com/biocommons/uta
2. The UniProt Consortium. UniProt: a worldwide hub of protein knowledge. Nucleic Acids Research. 2019;47:D506-D515.
3. Liu X, Wu C, Li C, and Boerwinkle E. dbNSFP v3.0: A one-stop database of functional predictions and annotations for human nonsynonymous and splice site SNVs. Human Mutation. 2015;37:235-241.
Liu X, Jian X, and Boerwinkle E. dbNSFP: A lightweight database of human nonsynonymous SNPs and their functional predictions. Human Mutation. 2011;32:894-899.
4. The AACR Project GENIE Consortium. AACR Project GENIE: powering precision medicine through an international consortium. Cancer Discovery. 2017;7(8):818-831. Dataset Version 8. This dataset does not represent the totality of the genetic landscape; see paper for more information.
5. All assertions and clinical trial landscape data are curated from primary sources. You can read more about the curation process here.