Difference between revisions of "Epidermal growth factor receptor inhibitors"

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'''Epidermal growth factor receptor inhibitors''', abbreviated '''EGFR inhibitors''', is a class of drugs that blocks the EGF receptor.
 
'''Epidermal growth factor receptor inhibitors''', abbreviated '''EGFR inhibitors''', is a class of drugs that blocks the EGF receptor.
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==EGFR==
 +
*EGFR (aka. ErbB1 or HER1) is a membranous receptor expressed in epithelial cells.
 +
*Most of activating mutations in [[NSCLC]] are in Exon 18-21 (kinase domain).
 +
*45% of the mutations are p.DEL19, approx 40-45% are p.L858R, approx 2% are p.T790M.
  
 
==Drugs==
 
==Drugs==
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*[[Gefitinib]] (''Iressa'', AstraZeneca).<ref name=pmid20855837/>  
 
*[[Gefitinib]] (''Iressa'', AstraZeneca).<ref name=pmid20855837/>  
 
*[[Erlotinib]] (''Tarceva'', Roche).<ref name=pmid20855837>{{cite journal |author=Sun Y, Ren Y, Fang Z, ''et al.'' |title=Lung adenocarcinoma from East Asian never-smokers is a disease largely defined by targetable oncogenic mutant kinases |journal=J. Clin. Oncol. |volume=28 |issue=30 |pages=4616–20 |year=2010 |month=October |pmid=20855837 |doi=10.1200/JCO.2010.29.6038 |url=}}</ref>
 
*[[Erlotinib]] (''Tarceva'', Roche).<ref name=pmid20855837>{{cite journal |author=Sun Y, Ren Y, Fang Z, ''et al.'' |title=Lung adenocarcinoma from East Asian never-smokers is a disease largely defined by targetable oncogenic mutant kinases |journal=J. Clin. Oncol. |volume=28 |issue=30 |pages=4616–20 |year=2010 |month=October |pmid=20855837 |doi=10.1200/JCO.2010.29.6038 |url=}}</ref>
*Afatinib (Gilotrif) - esp. effective when del19 is present.<ref>{{Cite journal  | last1 = Yang | first1 = JC. | last2 = Wu | first2 = YL. | last3 = Schuler | first3 = M. | last4 = Sebastian | first4 = M. | last5 = Popat | first5 = S. | last6 = Yamamoto | first6 = N. | last7 = Zhou | first7 = C. | last8 = Hu | first8 = CP. | last9 = O'Byrne | first9 = K. | title = 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. | journal = Lancet Oncol | volume = 16 | issue = 2 | pages = 141-51 | month = Feb | year = 2015 | doi = 10.1016/S1470-2045(14)71173-8 | PMID = 25589191 }}</ref>
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Second generation:
 
Second generation:
 
*Dacomitinib (''Vizimpro'', Pfizer) - not effective when EGFR T790M mutation present.<ref>{{Cite journal  | last1 = Mok | first1 = TS. | last2 = Cheng | first2 = Y. | last3 = Zhou | first3 = X. | last4 = Lee | first4 = KH. | last5 = Nakagawa | first5 = K. | last6 = Niho | first6 = S. | last7 = Lee | first7 = M. | last8 = Linke | first8 = R. | last9 = Rosell | first9 = R. | title = Improvement in Overall Survival in a Randomized Study That Compared Dacomitinib With Gefitinib in Patients With Advanced Non-Small-Cell Lung Cancer and EGFR-Activating Mutations. | journal = J Clin Oncol | volume =  | issue =  | pages = JCO2018787994 | month = Jun | year = 2018 | doi = 10.1200/JCO.2018.78.7994 | PMID = 29864379 }}</ref>
 
*Dacomitinib (''Vizimpro'', Pfizer) - not effective when EGFR T790M mutation present.<ref>{{Cite journal  | last1 = Mok | first1 = TS. | last2 = Cheng | first2 = Y. | last3 = Zhou | first3 = X. | last4 = Lee | first4 = KH. | last5 = Nakagawa | first5 = K. | last6 = Niho | first6 = S. | last7 = Lee | first7 = M. | last8 = Linke | first8 = R. | last9 = Rosell | first9 = R. | title = Improvement in Overall Survival in a Randomized Study That Compared Dacomitinib With Gefitinib in Patients With Advanced Non-Small-Cell Lung Cancer and EGFR-Activating Mutations. | journal = J Clin Oncol | volume =  | issue =  | pages = JCO2018787994 | month = Jun | year = 2018 | doi = 10.1200/JCO.2018.78.7994 | PMID = 29864379 }}</ref>
 +
*Afatinib (Gilotrif) - esp. effective when del19 is present.<ref>{{Cite journal  | last1 = Yang | first1 = JC. | last2 = Wu | first2 = YL. | last3 = Schuler | first3 = M. | last4 = Sebastian | first4 = M. | last5 = Popat | first5 = S. | last6 = Yamamoto | first6 = N. | last7 = Zhou | first7 = C. | last8 = Hu | first8 = CP. | last9 = O'Byrne | first9 = K. | title = 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. | journal = Lancet Oncol | volume = 16 | issue = 2 | pages = 141-51 | month = Feb | year = 2015 | doi = 10.1016/S1470-2045(14)71173-8 | PMID = 25589191 }}</ref>
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Third generation:
 
*Osimertinib <ref>{{Cite journal  | last1 = Alsharedi | first1 = M. | last2 = Bukamur | first2 = H. | last3 = Elhamdani | first3 = A. | title = Osimertinib for the treatment of patients with  | journal = Drugs Today (Barc) | volume = 54 | issue = 6 | pages = 369-379 | month = Jun | year = 2018 | doi = 10.1358/dot.2018.54.6.2817668 | PMID = 29998228 }}</ref>
 
*Osimertinib <ref>{{Cite journal  | last1 = Alsharedi | first1 = M. | last2 = Bukamur | first2 = H. | last3 = Elhamdani | first3 = A. | title = Osimertinib for the treatment of patients with  | journal = Drugs Today (Barc) | volume = 54 | issue = 6 | pages = 369-379 | month = Jun | year = 2018 | doi = 10.1358/dot.2018.54.6.2817668 | PMID = 29998228 }}</ref>
 
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*Nazartinib
  
 
Note:
 
Note:
*Both ''gefitinib'' and ''erlotinib'' are also classified as ''[[tyrosine kinase inhibitors]]'' (TKIs).
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*Both ''gefitinib'' and ''erlotinib'' are also classified as ''[[tyrosine kinase inhibitors]]'' (TKIs). After 10-12 months, tumors usu. develop resistencies.
  
 
==Use==
 
==Use==

Latest revision as of 04:50, 13 February 2020

Epidermal growth factor receptor inhibitors, abbreviated EGFR inhibitors, is a class of drugs that blocks the EGF receptor.

EGFR

  • EGFR (aka. ErbB1 or HER1) is a membranous receptor expressed in epithelial cells.
  • Most of activating mutations in NSCLC are in Exon 18-21 (kinase domain).
  • 45% of the mutations are p.DEL19, approx 40-45% are p.L858R, approx 2% are p.T790M.

Drugs

First generation:

Second generation:

  • Dacomitinib (Vizimpro, Pfizer) - not effective when EGFR T790M mutation present.[2]
  • Afatinib (Gilotrif) - esp. effective when del19 is present.[3]

Third generation:

  • Osimertinib [4]
  • Nazartinib

Note:

  • Both gefitinib and erlotinib are also classified as tyrosine kinase inhibitors (TKIs). After 10-12 months, tumors usu. develop resistencies.

Use

References

  1. 1.0 1.1 Sun Y, Ren Y, Fang Z, et al. (October 2010). "Lung adenocarcinoma from East Asian never-smokers is a disease largely defined by targetable oncogenic mutant kinases". J. Clin. Oncol. 28 (30): 4616–20. doi:10.1200/JCO.2010.29.6038. PMID 20855837.
  2. Mok, TS.; Cheng, Y.; Zhou, X.; Lee, KH.; Nakagawa, K.; Niho, S.; Lee, M.; Linke, R. et al. (Jun 2018). "Improvement in Overall Survival in a Randomized Study That Compared Dacomitinib With Gefitinib in Patients With Advanced Non-Small-Cell Lung Cancer and EGFR-Activating Mutations.". J Clin Oncol: JCO2018787994. doi:10.1200/JCO.2018.78.7994. PMID 29864379.
  3. Yang, JC.; Wu, YL.; Schuler, M.; Sebastian, M.; Popat, S.; Yamamoto, N.; Zhou, C.; Hu, CP. et al. (Feb 2015). "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.". Lancet Oncol 16 (2): 141-51. doi:10.1016/S1470-2045(14)71173-8. PMID 25589191.
  4. Alsharedi, M.; Bukamur, H.; Elhamdani, A. (Jun 2018). "Osimertinib for the treatment of patients with". Drugs Today (Barc) 54 (6): 369-379. doi:10.1358/dot.2018.54.6.2817668. PMID 29998228.