Practical management of patients with Tarceva

1
Practical management of patients with Tarceva

• Romàn Pérez-Soler
• Montefiore Medical CenterAlbert Einstein College
  of Medicine,Bronx, New York, USA

2
Adverse events (AEs) observed inBR.21 study ()
Tarceva Summary of Product Characteristics, F.
Hoffmann-La Roche, 2007
3
Routine clinical practice with Tarceva confirms
clinical trial results
100 80 60 40 20 0
Incidence of toxicity ()
BR.211(n727)
TRUST2(n5,378)
Rash
1Tarceva Summary of Product Characteristics, F.
Hoffmann-La Roche, 2007 2Gatzemeier U, et al. J
Clin Oncol 200725(Suppl. 18 Pt I)420s (Abs.
7645)
4
Management of diarrhoea

• In most cases, diarrhoea can be managed with
  loperamide

Recommended regimen 4mg loperamide at onset of
symptoms, followed by 2mg every 24 hours until
patient has remained free of diarrhoea for 12
hours

• Appropriate re-hydration should be provided
• In cases of severe diarrhoea that is unresponsive
  to loperamide, erlotinib dose reduction or delay
  may be necessary
• Ensure that patients seek medical advice early

Tarceva Summary of Product Characteristics, F.
Hoffmann-La Roche, 2007
5
EGFR inhibitor-associated rash

• Rash is a common toxicity of all EGFR inhibitors

Rash with Tarceva

• Generally develops within710 days of starting
  therapy

• May spontaneously resolveand reappear

• Is reversible following drug discontinuation

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Practical grading of rash
Grade 1
Grade 2
Grade 3/4

• Generally localised to face/upper trunk
• Minimally symptomatic
• No impact on daily activities
• No sign of superinfection

• More generalised
• Moderately symptomatic
• Minimal impact on daily activities
• No sign of superinfection

• More generalised
• Severely symptomatic
• Significant impact on daily activities
• Superinfection not uncommon

Lynch TJ, et al. Oncologist 20071261021
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Practical grading of rash
Ensure correct dosing 1 hour before or 2 hours
after eating
Preventive measures From start of therapy twice
daily application of alcohol-free emollient cream
to entire body, and sunscreen to exposed skin
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Management recommendations for symptomatic rash
(panel consensus)

• Treat as moderate
• AND
• Systemic steroids
• AND
• Consider dose delay

• Synthetic tetracycline

• No treatment

OR
AND

• Hydrocortisone2.5 cream
• OR
• Antibiotic gel

• Hydrocortisone1 or 2.5 cream
• AND/OR
• Antibiotic gel

2-weekly assessments
Doxycycline or minocycline 100mg
bid Prednisone, methylprednisolone 30mg once
daily (tapered over 30 days)
Lynch TJ, et al. Oncologist 20071261021
9
Rash versus overall survival on Tarceva in BR.21

• Excludes patients who died within 28 days of entry

Grade 0 (n86)Median 3.3 months Grade 1
(n135)Median 7.1 months Grade 2
(n223)Median 11.1 months
1.0 0.75 0.50 0.25 0
Survival probability
0 6 12 18 24 30 36
Survival (months)

• Correlation was maintained in multivariate
  analyses

Wacker B, et al. Clin Cancer Res 200713391321
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Conclusions

• Rash and diarrhoea are the most common toxicities
  associated with Tarceva therapy
• usually mild or moderate
• generally do not lead to dose reduction or
  withdrawal
• Diarrhoea easily managed by standard methods
• Preventive measures recommended for rash
• Active rash management should allow patients to
  continue Tarceva
• dose reduction/delay should only be considered as
  a last resort