Searching On:

Disease:

Gene:

Lung Cancer, EGFR

View:
Expand Collapse Lung Cancer  - General Description This year about 226,000 people in the U.S. will be told by a doctor that they have lung cancer. However, about 390,000 Americans remain alive today after having been diagnosed with this malignancy. Lung cancer includes tumors that begin in tissues lining air passages inside the lungs and bronchi. The bronchi are the 2 branches of the windpipe (trachea) that lead to the lungs. Based on how the cells look under a microscope, lung cancers are divided into 2 main types: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). NSCLC accounts for 85% of these cases.

The main subtypes of NSCLC are squamous cell carcinoma (cancer beginning in thin, flat scaly-looking cells), adenocarcinoma (cancer beginning in cells that make mucus and other substances) and large cell carcinoma (cancer beginning in several types of large cells). The 2 main types of SCLC are small cell carcinoma (oat cell cancer) and combined small cell carcinoma.

Lung cancer (and other tumors) can spread (metastasize) from the place where it started (the primary tumor) in 3 ways. First, it can invade the normal tissue surrounding it. Second, cancer cells can enter the lymph system and travel through lymph vessels to distant parts of the body. Third, the cancer cells can get into the bloodstream and go to other places in the body. In these distant places, the cancer cells cause secondary tumors to grow. The main sites to which lung cancer spreads are the adrenal gland, liver and lungs.

To find out whether the cancer has entered the lymph system, a surgeon removes all or part of a node near the primary tumor and a pathologist looks at it through a microscope to see if cancer cells are present. Several kinds of imaging also can be performed to determine if the cancer has spread. These include MRI, bone scans and endoscopic ultrasound (EUS).

The FDA has approved several targeted therapies to treat patients with NSCLC. These include bevacizumab (Avastin), cetuximab (Erbitux), erlotinib (Tarceva), gefitnib (Iressa) and crizotinib (Xalkori). So far there are no FDA-approved targeted therapies for SCLC.

Despite significant improvements in the treatment of lung cancers, novel therapies and treatment strategies are needed.

Source: National Cancer Institute, 2012
Estimated new cases and deaths from lung cancer (non-small cell and small cell combined) in the United States in 2012:

New cases: 226,160
Deaths: 160,340

Lung cancer is the leading cause of cancer-related mortality in the United States. The 5-year relative survival rate from 1995 to 2001 for patients with lung cancer was 15.7%. The 5-year relative survival rate varies markedly depending on the stage at diagnosis, from 49% to 16% to 2% for patients with local, regional and distant stage disease, respectively.

NSCLC arises from the epithelial cells of the lung, from the central bronchi to the terminal alveoli. The histological type of NSCLC correlates with the site of origin, reflecting the variation in respiratory tract epithelium from the bronchi to the alveoli. Squamous cell carcinoma usually starts near a central bronchus while adenocarcinoma usually originates in peripheral lung tissue.

Tobacco smoking is the strongest risk factor for developing lung cancer, though it should be noted that the majority of patients diagnosed with lung cancer quit smoking years prior to diagnosis or were never-smokers (up to 15% of cases).

The identification of driver oncogene mutations in lung cancer has led to the development of targeted therapy that has vastly broadened treatment options and improved outcomes for subsets of patients with metastatic disease. It is now common practice to determine the genotype of a NSCLC patient early in the course of their diagnosis, to ensure that all possible treatment options are considered.

Source: National Cancer Institute, 2012
This year about 226,000 people in the U.S. will be told by a doctor that they have lung cancer. However, about 390,000 Americans remain alive today after having been diagnosed with this malignancy. Lung cancer includes tumors that begin in tissues lining air passages inside the lungs and bronchi. The bronchi are the 2 branches of the windpipe (trachea) that lead to the lungs. Based on how the cells look under a microscope, lung cancers are divided into 2 main types: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). NSCLC accounts for 85% of these cases.

The main subtypes of NSCLC are squamous cell carcinoma (cancer beginning in thin, flat scaly-looking cells), adenocarcinoma (cancer beginning in cells that make mucus and other substances) and large cell carcinoma (cancer beginning in several types of large cells). The 2 main types of SCLC are small cell carcinoma (oat cell cancer) and combined small cell carcinoma.

Lung cancer (and other tumors) can spread (metastasize) from the place where it started (the primary tumor) in 3 ways. First, it can invade the normal tissue surrounding it. Second, cancer cells can enter the lymph system and travel through lymph vessels to distant parts of the body. Third, the cancer cells can get into the bloodstream and go to other places in the body. In these distant places, the cancer cells cause secondary tumors to grow. The main sites to which lung cancer spreads are the adrenal gland, liver and lungs.

To find out whether the cancer has entered the lymph system, a surgeon removes all or part of a node near the primary tumor and a pathologist looks at it through a microscope to see if cancer cells are present. Several kinds of imaging also can be performed to determine if the cancer has spread. These include MRI, bone scans and endoscopic ultrasound (EUS).

The FDA has approved several targeted therapies to treat patients with NSCLC. These include bevacizumab (Avastin), cetuximab (Erbitux), erlotinib (Tarceva), gefitnib (Iressa) and crizotinib (Xalkori). So far there are no FDA-approved targeted therapies for SCLC.

Despite significant improvements in the treatment of lung cancers, novel therapies and treatment strategies are needed.

Source: National Cancer Institute, 2012
Estimated new cases and deaths from lung cancer (non-small cell and small cell combined) in the United States in 2012:

New cases: 226,160
Deaths: 160,340

Lung cancer is the leading cause of cancer-related mortality in the United States. The 5-year relative survival rate from 1995 to 2001 for patients with lung cancer was 15.7%. The 5-year relative survival rate varies markedly depending on the stage at diagnosis, from 49% to 16% to 2% for patients with local, regional and distant stage disease, respectively.

NSCLC arises from the epithelial cells of the lung, from the central bronchi to the terminal alveoli. The histological type of NSCLC correlates with the site of origin, reflecting the variation in respiratory tract epithelium from the bronchi to the alveoli. Squamous cell carcinoma usually starts near a central bronchus while adenocarcinoma usually originates in peripheral lung tissue.

Tobacco smoking is the strongest risk factor for developing lung cancer, though it should be noted that the majority of patients diagnosed with lung cancer quit smoking years prior to diagnosis or were never-smokers (up to 15% of cases).

The identification of driver oncogene mutations in lung cancer has led to the development of targeted therapy that has vastly broadened treatment options and improved outcomes for subsets of patients with metastatic disease. It is now common practice to determine the genotype of a NSCLC patient early in the course of their diagnosis, to ensure that all possible treatment options are considered.

Source: National Cancer Institute, 2012
Expand Collapse EGFR  - General Description
CLICK IMAGE FOR MORE INFORMATION
The EGFR gene encodes for a cell-surface protein known as the epidermal growth factor receptor, which is found in many normal epithelial tissues such as the skin and hair follicles. When members of the epidermal growth factor family attach to EGFR, they activate several different cell signaling pathways that control various cell functions, including cell growth.

Mutations in EGFR can lead to unregulated activation of the protein. These types of activating mutations are often found in NSCLC (non-small cell lung cancer), glioblastoma and head and neck squamous cell carcinoma. Sometimes, excess EGFR protein is produced due to the presence of too many copies of the EGFR gene, leading to excessive cell division and growth in the presence of epidermal growth factor. Among the human cancers in which EGFR overabundance is present are cancers of the head and neck (squamous cell), colon, rectum, lung (NSCLC), central nervous system (glioblastoma), pancreas and breast (HER2-positive metastatic). Blocking EGFR in tumors may keep cancer cells from growing. The FDA has approved several therapies that target EGFR in one or more cancers.

Tumor mutation profiling performed clinically at the MGH Cancer Center has indicated that EGFR mutations occur primarily in lung cancer (~15%), but also in a minor subset of gastric (2%), brain (1%) and pancreatic (1%) cancers.

Source: Genetics Home Reference
The epidermal growth factor receptor (EGFR) gene encodes for a cell-surface protein that belongs to the ERBB family of receptor tyrosine kinases. Four members of the ERBB family have been identified: EGFR (ERBB1, HER1), ERBB2 (HER2), ERBB3 (HER3) and ERBB4 (HER4). Binding of a ligand induces ERBB receptor homo-/hetero-dimerization and triggers a signaling cascade that drives many cellular responses. These include the activation of PI3K-AKT/mTOR and MAP kinase/ERK pathways, which promote cell survival and proliferation. EGFR mutations have been most frequently associated with non-small cell lung cancer, but have also been described in other malignancies including gliomas, head and neck, prostate and ovarian tumors.

Tumor mutation profiling performed clinically at the MGH Cancer Center has indicated that EGFR mutations occur primarily in lung cancer (~15%), but also in a minor subset of gastric (2%), brain (1%) and pancreatic (1%) cancers.

Source: Genetics Home Reference
PubMed ID's
15864276, 15118073, 15118125, 15329413, 18772890, 15837736, 16720329, 21057220
Expand Collapse EGFR  in Lung Cancer
There is a clear association between the presence of certain activating EGFR mutations in lung cancer and high response rates to certain tyrosine kinase inhibitors. In 2013, the FDA approved the use of both erlotinib (Tarceva) and afatinib (Gilotrif) for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have EGFR exon 19 deletions or exon 21 (L858R) mutations identified using an approved diagnostic test.

Currently, the FDA-approved use of erlotinib or afatinib in the treatment of metastatic non-small cell lung cancer is restricted to the presence of the EGFR exon 19 and L858R mutations in the patient’s tumor. Clinical trials are now investigating novel inhibitors that are active across a number of ERBB family members (EGFR, HER2, HER3, HER4) and have reported increased response rates in tumors that carry rare EGFR mutations.

The EGFR T790M mutation can develop in a patient’s lung tumor during the course of treatment with a conventional targeted EGFR therapy (such as erlotinib or gefitinib), which then promotes resistance to that particular therapy. While afatinib has not shown any benefit, current clinical evaluations are determining whether other new generation EGFR small molecule inhibitors can provide therapeutic benefits in the treatment of EGFR-mutant NSCLC patients who had previously relapsed on erlotinib and/or gefitinib.

EGFR mutations occur almost exclusively in adenocarcinoma and may impart a more favorable prognosis when compared to patients without EGFR mutations. The presence of EGFR mutations predicts a better outcome for lung cancer patients, regardless of treatment received. These mutations are mainly found in patients with a low smoking history (incidence of 50% among U.S. non-smokers with lung cancer) and those of Asian ethnicity (incidence of up to 75% in Japanese non-smokers with lung cancer).

There is a clear association between the presence of certain activating EGFR mutations in lung cancer and high response rates to certain tyrosine kinase inhibitors. In 2013, the FDA approved the use of both erlotinib (Tarceva) and afatinib (Gilotrif) for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have EGFR exon 19 deletions or exon 21 (L858R) mutations identified using an approved diagnostic test.

Currently, the FDA-approved use of erlotinib or afatinib in the treatment of metastatic non-small cell lung cancer is restricted to the presence of the EGFR exon 19 and L858R mutations in the patient’s tumor. Clinical trials are now investigating novel inhibitors that are active across a number of ERBB family members (EGFR, HER2, HER3, HER4) and have reported increased response rates in tumors that carry rare EGFR mutations.

The EGFR T790M mutation can develop in a patient’s lung tumor during the course of treatment with a conventional targeted EGFR therapy (such as erlotinib or gefitinib), which then promotes resistance to that particular therapy. While afatinib has not shown any benefit, current clinical evaluations are determining whether other new generation EGFR small molecule inhibitors can provide therapeutic benefits in the treatment of EGFR-mutant NSCLC patients who had previously relapsed on erlotinib and/or gefitinib.

EGFR mutations occur almost exclusively in adenocarcinoma and may impart a more favorable prognosis when compared to patients without EGFR mutations. The presence of EGFR mutations predicts a better outcome for lung cancer patients, regardless of treatment received. These mutations are mainly found in patients with a low smoking history (incidence of 50% among U.S. non-smokers with lung cancer) and those of Asian ethnicity (incidence of up to 75% in Japanese non-smokers with lung cancer).

PubMed ID's
17189394, 20887192, 17904685, 16204070, 20808254, 18199554, 17349580, 17233841, 16205628, 16043828, 18626007, 17410005, 16314000, 17318210, 17075123, 16204011, 20038723, 19692680, 16014883, 15998907, 18322248, 21252719, 15604253, 16187797, 23816967, 23816963
Expand Collapse No mutation selected
The mutation of a gene provides clinicians with a very detailed look at your cancer. Knowing this information could change the course of your care. To learn how you can find out more about genetic testing please visit http://www.massgeneral.org/cancer/news/faq.aspx or contact the Cancer Center.
Our Lung Cancer Team

Share with your Physican

Print information for your Physician.

Print information

Your Matched Clinical Trials

Trial Matches: (D) - Disease, (G) - Gene
Trial Status: Showing Results: 1-10 of 45 Per Page:
12345Next »
Protocol # Title Location Status Match
NCT02108964 A Phase I/II, Multicenter, Open-label Study of EGFRmut-TKI EGF816, Administered Orally in Adult Patients With EGFRmut Solid Malignancies A Phase I/II, Multicenter, Open-label Study of EGFRmut-TKI EGF816, Administered Orally in Adult Patients With EGFRmut Solid Malignancies MGH Open DG
NCT02365662 A Study Evaluating Safety and Pharmacokinetics of ABBV-221 in Subjects With Advanced Solid Tumor Types Likely to Exhibit Elevated Levels of Epidermal Growth Factor Receptor A Study Evaluating Safety and Pharmacokinetics of ABBV-221 in Subjects With Advanced Solid Tumor Types Likely to Exhibit Elevated Levels of Epidermal Growth Factor Receptor MGH Open DG
NCT02716116 A Trial of AP32788 in Non-Small Cell Lung Cancer A Trial of AP32788 in Non-Small Cell Lung Cancer MGH Open DG
NCT01746251 Adjuvant Afatinib in Stage I-III NSCLC With EGFR Mutation Adjuvant Afatinib in Stage I-III NSCLC With EGFR Mutation MGH Open DG
NCT01553942 Afatinib With CT and RT for EGFR-Mutant NSCLC Afatinib With CT and RT for EGFR-Mutant NSCLC MGH Open DG
NCT02193282 Erlotinib Hydrochloride in Treating Patients With Stage IB-IIIA Non-small Cell Lung Cancer That Has Been Completely Removed by Surgery (An ALCHEMIST Treatment Trial) Erlotinib Hydrochloride in Treating Patients With Stage IB-IIIA Non-small Cell Lung Cancer That Has Been Completely Removed by Surgery (An ALCHEMIST Treatment Trial) MGH Open DG
NCT02520778 Osimertinib and Navitoclax in Treating Patients With EGFR-Positive Previously Treated Advanced or Metastatic Non-small Cell Lung Cancer Osimertinib and Navitoclax in Treating Patients With EGFR-Positive Previously Treated Advanced or Metastatic Non-small Cell Lung Cancer MGH Open DG
NCT02437136 Ph1b/2 Dose-Escalation Study of Entinostat With Pembrolizumab in NSCLC With Expansion Cohorts in NSCLC and Melanoma Ph1b/2 Dose-Escalation Study of Entinostat With Pembrolizumab in NSCLC With Expansion Cohorts in NSCLC and Melanoma MGH Open DG
NCT02052778 A Dose Finding Study Followed by a Safety and Efficacy Study in Patients With Advanced Solid Tumors or Multiple Myeloma With FGF/FGFR-Related Abnormalities A Dose Finding Study Followed by a Safety and Efficacy Study in Patients With Advanced Solid Tumors or Multiple Myeloma With FGF/FGFR-Related Abnormalities MGH Open D
NCT02637531 A Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IPI-549 A Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IPI-549 MGH Open D
Trial Status: Showing Results: 1-10 of 45 Per Page:
12345Next »
Our Lung Cancer Team

Share with your Physican

Print information for your Physician.

Print information