The growth-factor-receptor tyrosine kinase family includes EGFR (ErbB1, HER1), ErbB2 (HER2, neu in rodents), ErbB3 (HER3), and ErbB4 (HER4).1 Receptor overexpression and ligand-dependent and ligand-independent mechanisms can cause abnormal EGFR activation.
When EGFR is overexpressed it contributes to tumorigenesis, driving aggressive cell growth.2 It is recognized as a biomarker of resistance in tumors.
Understanding the Role of EGFR
Expression in Cancer
EGFR overexpression is associated with a variety of cancer types. The graphic below displays the expression of EGFR in up to a certain percentage of cases in each cancer type. Sources for these numbers can be found in the references link above.
EGFR Inhibitors
EGFR inhibitors bind to certain parts of the EGFR protein, thus slowing or stopping the growth of cancer cells. This table outlines therapies targeting EGFR both approved by the FDA and in the pipeline.
EGFR Inhibitors Approved by the FDAa |
|
Brand Name (Generic Drug Name) |
Indications |
Caprelsa (vandetanib)1 |
Treatment of symptomatic or progressive medullary thyroid cancer in patients with unresectable, locally advanced, or metastatic disease |
Erbitux (cetuximab)2 |
In combination with radiation therapy for the treatment of patients with locally or regionally advanced head and neck squamous cell carcinoma |
In combination with fluorouracil for the treatment of patients with recurrent locoregional or metastatic squamous cell carcinoma of the head and neck |
|
Treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma of the head and neck that progressed after platinum-based therapy |
|
In combination with FOLFIRI for the first-line treatment of patients with K-RAS wild-type, EGFR-expressing, metastatic CRC determined by an FDA-approved test |
|
In combination with irinotecan for the treatment of patients with K-RAS wild-type, EGFR-expressing, metastatic CRC refractory to irinotecan-based chemotherapy, as determined by an FDA-approved test |
|
Treatment of patients with K-RAS wild-type, EGFR-expressing, metastatic CRC unresponsive to oxaliplatin- and irinotecan-based chemotherapy or for patients who are intolerant to irinotecan |
|
Treatment of patients with K-RAS wild-type, EGFR-expressing, metastatic CRC who are intolerant to irinotecan |
|
In combination with encorafenib for the treatment of adults with metastatic, BRAF V600E mutation-positive CRC determined by an FDA-approved test who have received prior therapy |
|
Exkivity (mobocertinib)3 |
Treatment of adults with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations determined by an FDA-approved test that progressed during or after platinum-based chemotherapy |
Gilotrif (afatinib)4 |
First-line treatment of patients with metastatic NSCLC with non-resistant EGFR mutations detected by an FDA-approved test |
Treatment of patients with metastatic, squamous NSCLC that progressed after platinum-based chemotherapy |
|
Iressa (gefitinib)5 |
First-line treatment of patients with metastatic NSCLC with EGFR exon 19 deletions or exon 21 (L858R) substitution mutations detected by an FDA-approved test |
Portrazza (necitumumab)6 |
In combination with gemcitabine and cisplatin for the first-line treatment of patients with metastatic, squamous NSCLC |
Tagrisso (osimertinib)7 |
Adjuvant therapy after tumor resection in adults with NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test |
First-line treatment of adults with metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test |
|
Treatment of adults with metastatic EGFR T790M mutation-positive NSCLC, as detected by an FDA-approved test, that progressed during or after EGFR TKI therapy |
|
Tarceva (erlotinib)8 |
Treatment of patients with metastatic NSCLC with EGFR exon 19 deletions or exon 21 (L858R) substitution mutations detected by an FDA-approved test receiving first-line, maintenance, or second- or greater-line treatment after progression with at least 1 prior chemotherapy regimen |
In combination with gemcitabine for the first-line treatment of patients with locally advanced, unresectable, or metastatic pancreatic cancer |
|
Vectibix (panitumumab)9 |
In combination with FOLFOX for the first-line treatment of patients with metastatic, wild-type RAS CRC |
Treatment of patients with metastatic, wild-type RAS CRC that progressed with fluoropyrimidine, oxaliplatin, and irinotecan-containing chemotherapy |
|
Vizimpro (dacomitinib)10 |
First-line treatment of patients with metastatic NSCLC with EGFR exon 19 deletion or exon 21 L858R substitution mutations detected by an FDA-approved test |
EGFR Inhibitors in the Pipelineb |
|
Generic Drug Name |
Potential Indications |
BCA10111 |
Being evaluated for the treatment of patients with cutaneous squamous cell carcinoma; in combination with pembrolizumab for the treatment of patients with head and neck squamous cell carcinoma and squamous carcinoma of the anal canal |
EQ143, HS-10296 (aumolertinib)12 |
Being evaluated for the treatment of patients with EGFR-mutated NSCLC |
Furmonertinib13 |
Being evaluated for the treatment of patients with advanced or metastatic NSCLC |
Tagrisso (osimertinib)14 |
Being evaluated in combination with Koselugo or Orpathys for advanced EGFR-mutant NSCLC; in combination with CTx FLAURA2 for the first-line treatment of advanced EGFR-mutant NSCLC; in combination with Orpathys for advanced EGFR-mutant NSCLC; in combination with Orpathys for advanced EGFR-mutant NSCLC; in combination with CTx for the neoadjuvant treatment of stage II/III resectable EGFR-mutant NSCLC; for the adjuvant treatment of EGFR-mutant NSCLC; for the adjuvant treatment of stage Ia2-Ia3 EGFR-mutant NSCLC after complete tumor resection; for the treatment of stage III EGFR-mutant NSCLC; for the second-line treatment of EGFR-mutant, osimertinib-resistant NSCLC |
CRC, colorectal cancer; EGFR, epidermal growth factor receptor; FOLFIRI, leucovorin calcium (calcium folinate), 5-fluorouracil, and irinotecan; FOLFOX, leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin; NSCLC, non-small-cell lung cancer.
aAdapted from prescribing information.1-10 b Adapted from manufacturer websites.11-14 |