EGFR Inhibitors

Question 1

What drugs are in the EGFR Inhibitors class?

Answer 1

Drugs in this class are (not all inclusive):
- Gefitinib
- Erlotinib
- Osimertinib
- Afatinib

Question 2

What is the brand name of Gefitinib?

Answer 2

The brand name of this generic drug is:
- Iressa

Question 3

What is the brand name of Erlotinib?

Answer 3

The brand name of this generic drug is:
- Tarceva

Question 4

What is the brand name of Osimertinib?

Answer 4

The brand name of this generic drug is:
- Tagrisso

Question 5

What is the brand name of Afatinib?

Answer 5

The brand name of this generic drug is:
- Gilotrif

Question 6

What is the generic of name of Iressa?

Answer 6

The generic name of this brand name drug is:
- Gefitinib

Question 7

What is the generic of name of Tarceva?

Answer 7

The generic name of this brand name drug is:
- Erlotinib

Question 8

What is the generic of name of Tagrisso?

Answer 8

The generic name of this brand name drug is:
- Osimertinib

Question 9

What is the generic of name of Gilotrif?

Answer 9

The generic name of this brand name drug is:
- Afatinib

Question 10

What are the main indications for use of Gefitinib?

Answer 10

The main indications of this drug are:
- Non-Small Cell Lung Cancer with EGFR mutation

Question 11

What are the main indications for use of Erlotinib?

Answer 11

The main indications of this drug are:
- Non-Small Cell Lung Cancer with EGFR mutation
- Pancreatic Cancer with EGFR mutation

Question 12

What are the main indications for use of Osimertinib?

Answer 12

The main indications of this drug are:
- Non-Small Cell Lung Cancer with EGFR mutation, T790M EGFR-mutation positive, or brain/leptomeningeal metastases

Question 13

What are the main indications for use of Afatinib?

Answer 13

The main indications of this drug are:
- Non-Small Cell Lung Cancer with EGFR mutation

Question 14

What are the main/common indications of the EGFR Inhibitors class?

Answer 14

The main/common indications of this drug class are:
- Certain cancers (such as Non-Small Cell Lung Cancer) with EGFR mutation

Question 15

What is the class and MOA of Gefitinib?

Answer 15

This drug in the following class:
- EGFR Inhibitors

This drug’s MOA is as follows:
- EGFR inhibitors are highly selective tyrosine kinase inhibitors that covalently bind to epidermal growth factor receptors and irreversibly inhibit tyrosine kinase phosphorylation and downregulate EGFR signaling preventing cell growth.

Question 16

What is the class and MOA of Erlotinib?

Answer 16

This drug in the following class:
- EGFR Inhibitors

This drug’s MOA is as follows:
- EGFR inhibitors are highly selective tyrosine kinase inhibitors that covalently bind to epidermal growth factor receptors and irreversibly inhibit tyrosine kinase phosphorylation and downregulate EGFR signaling preventing cell growth.

Question 17

What is the class and MOA of Osimertinib?

Answer 17

This drug in the following class:
- EGFR Inhibitors

This drug’s MOA is as follows:
- EGFR inhibitors are highly selective tyrosine kinase inhibitors that covalently bind to epidermal growth factor receptors and irreversibly inhibit tyrosine kinase phosphorylation and downregulate EGFR signaling preventing cell growth.

Question 18

What is the class and MOA of Afatinib?

Answer 18

This drug in the following class:
- EGFR Inhibitors

This drug’s MOA is as follows:
- EGFR inhibitors are highly selective tyrosine kinase inhibitors that covalently bind to epidermal growth factor receptors and irreversibly inhibit tyrosine kinase phosphorylation and downregulate EGFR signaling preventing cell growth.

Question 19

What are the notable/common monitoring parameters for the EGFR Inhibitors class?

Answer 19

The notable/common monitoring parameters for this drug class are:
- Confirm EGFR mutation positive before beginning therapy

Question 20

Describe the emetic potential of the EGFR Inhibitors class.

Answer 20

The emetic potential of this drug class is:
- Minimal-Low

Question 21

Describe the administration of Gefitinib.

Answer 21

The administration of this drug is described as follows:
- Oral

Question 22

Describe the administration of Erlotinib.

Answer 22

The administration of this drug is described as follows:
- Oral
- Absorption is ~60% on an empty stomach, increases to ~100% with food

Question 23

Describe the administration of Osimertinib.

Answer 23

The administration of this drug is described as follows:
- Oral

Question 24

Describe the administration of Afatinib.

Answer 24

The administration of this drug is described as follows:
- Oral
- Absorption is decreased with high-fat meals

Question 25

Describe the metabolism of EGFR Inhibitors.

Answer 25

The metabolism of this drug class is as follows: - Primarily hepatic with the exception of Afatinib (minimal enzymatic metabolism)

Question 26

What are the notable/common ADRs of the EGFR Inhibitors class?

Answer 26

The notable/common ADRs of this drug class are: - Acneiform Rash - N/V/D - Skin/nail changes - Dry mouth - Decreased appetite - Hepatic dysfunction - Disease flare (after discontinuation)

Question 27

Describe the strategy and rationale for management of Acneiform Rash caused by EGFR Inhibitors.

Answer 27

The strategy and rationale for management of this condition caused by this drug are: - This is a common side effect of this class. - EGFR is expressed in many different tissues, including epithelial tissue, skin, hair follicles, and the gastrointestinal tract. - During treatment with EGFR inhibitors cutaneous adverse events occur in 65-90% of patients. This rash usually develops in the first 1-2 weeks, peaks at 3-4 weeks of therapy, and its intensity decreases after 2 weeks but can often persist over some months. - Management: - Mild Rash: patients may not require any form of intervention. Consider topical hydrocortisone cream or clindamycin gel. - Moderate Rash: hydrocortisone cream or clindamycin gel plus doxycycline 100 mg oral twice daily or minocycline 100 mg oral twice daily. - Studies have found that the development of a rash seems to be associated with an increased likelihood of tumor response and/or survival in NSCLC.

Question 28

What are the clinical pearls of the EGFR Inhibitors class?

Answer 28

The clinical pearls of this drug class are as follows: - For patients with asymptomatic progression on a TKI, continuation of EGFR-TKI therapy can be considered - For patients who have not received osimertinib, recommend testing for the T790M mutation at time of progression. - If positive, osimertinib therapy is indicated. - For patients with symptomatic progression on a TKI, options include: - Continuing with an EGFR inhibitor - Switching to osimertinib if T790M mutation positive - Switching to systemic chemotherapy - EGFR mutations are present in 10-15% of non-small cell lung cancers and typically occur more commonly in women, Asian ethnicities, and never-smokers. - K-RAS and EGFR mutations are mutually exclusive. Meaning that if a patient has a K-RAS mutation, they will not respond to EGFR inhibitors.

Question 29

Describe resistance among EGFR Inhibitors?

Answer 29

Resistance to this drug class is as follows: - The T790M mutation is the most common EGFR resistance mechanism (seen in 50-60% of patients) and can be present at diagnosis or develop during treatment. - This mutation increases affinity of kinase to ATP and decreases affinity to erlotinib and gefitinib. - Patients with the T790M mutation should be switched to osimertinib as is a third-generation EGFR-TKI that is selective for both EGFR-TKI-sensitizing and T790M resistance mutations.