2. Tarceva
• Generic name: Erlotinib
• Brand name: Tarceva®
• FDA Approval Date: November 18,
2004
3. Tarceva
• Indicated for :the treatment of locally
advanced or metastatic non-small cell
lung cancer that has failed prior
chemotherapy
• Human Epidermal Growth Factor
Receptor Type 1/Epidermal Growth
Factor Receptor (HER1/EGFR) tyrosine
kinase inhibitor
• Inhibits intracellular phosphorylation of
tyrosine kinase associated with EGFR
Introduction
4. Introduction
• Lung Cancer
– Non-Small Cell Lung Cancer
– Stage of Non-Small Cell Lung Cancer
• Tarceva in action
– Cancer cell proliferation
– HER family of receptors and the role of
HER1/EGFR
– Dysregulation of HER1/EGFR
– Tarceva mechanism of inhibition
Introduction
5. Lung Cancer
• Two general types of lung cancer
exist:
– Non-small cell lung cancer (NSCLC)
– Small cell lung cancer
• The most common type
of lung cancer is NSCLC.
Approximately 147,000
new cases of NSCLC were
reported in the United States in 2004.
Introduction
6. Main types of NSCLC
• There are three main
types of NSCLC:
– Adenocarcinoma
(including
bronchioloalveolar
carcinoma)
– Squamous cell
carcinoma
– Large cell
undifferentiated
carcinoma
Introduction
9. Tarceva in action
• Cancer cell proliferation
• The Human Epidermal Receptor
(HER) family of receptors
and the role of HER1/Epidermal
Growth Factor Receptor (EGFR)
• Dysregulation of HER1/EGFR
• Tarceva mechanism of inhibition
Introduction
17. Pharmacokinetics
• A: bioavailability ≈ 60%; food ↑
bioavailability to almost 100%
• D: ≈ 93% protein bound to albumin
and alpha-1 acid glycoprotein
• M: primarily by CYP3A4 and to a
lesser extent by CYP1A2
• E: mainly fecal (> 80%); t½= 36h
Introduction
18. Drug Interactions
• CYP3A4 inhibitors expected to
increase exposure to erlotinib:
ketoconazole increased AUC by
67%
• CYP3A4 inducers expected to
decrease exposure to erlotinib:
rifampicin increased clearance by
3-fold and reduced AUC by 67%
20. Monitoring
• Monitor for acute onset of new or
progressive pulmonary symptoms
such as dyspnea, cough, or fever
• If interstitial lung disease is
diagnosed, discontinue erlotinib
• Consider dose adjustment with
severe LFT changes (AST,ALT, Bili,
Alk Phos)
21. Prescription Information
• Standard dose is 150 mg po daily
taken at least one hour before or
two hours after the ingestion of
food
• Cost: #30 150 mg tablets $2125.02
22. Clinical studies :Tarceva: BR.21
Tarceva: BR.21
Target
enrolment
700 patients; stage IIIB or IV NSCLC
Prior therapy 1 or 2 chemotherapy regimens
Design Randomised 2:1
Tarceva 150mg/day plus BSC vs Placebo
plus BSC
Primary
endpoint
Overall survival
Secondary
endpoints
Progression-free survival
Symptom deterioration
Response rate
Tolerability
Tissue HER1/EGFR vs outcome/safety
28. BR.21 Summary
• In patients who have failed standard
chemotherapy for NSCLC, erlotinib
significantly improves
– Response rates and progression free
survival
– Overall survival
– Disease related QoL and overall QoL
• Prolongation of survival was seen in
most subsets of patients
29. Summary
• Tarceva™, erlotinib, is a Human Epidermal
Growth Receptor Type 1/ Epidermal growth
Factor Receptor (HER1/EGFR) tyrosine
kinase inhibitor.
• Tarceva™ is indicated for the treatment of
patients with locally advanced or metastatic
nonsmall cell lung cancer (NSCLC) after
failure of at least one prior chemotherapy
regimen.
30. Summary
• Dermatologic and GI side effects are
common.
• The incidence of Interstitial Lung
Disease was the same as the placebo
group (0.8%) in one trial.
31. References
1. http://www.tarceva,com. Accessed on
2/27/05
2. Tarceva™ package insert. Genentech. 2004
Downloaded from www.tarceva.com 2/27/05
3. http://www.drugstore.com. Accessed on
3/6/05