heinshansen.ppt
TRANSCRIPT
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Second-line treatment in action
Heine HansenNational University Hospital, Copenhagen, Denmark
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Case study 1
Case kindly provided by:
Dr Wolfgang Schütte
Städtisches Krankenhaus Martha-Maria Halle Dölau, Germany
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Case study 1
• 78-year-old female, Caucasian, non-smoker; PS 2
• Poorly-differentiated adenocarcinoma– stage T3N2M0 (IIIA)
• Three cycles vinorelbine/carboplatin: no remission
• General physical condition considered too poor for second-line chemotherapy
• Treatment with Tarceva 150mg/day was initiated
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Case study 1 (cont’d)
After 2 months of Tarceva (complete remission)
PS 0
Start of treatment
PS 2
Striking tumour response and clinical improvement How long should treatment be maintained?
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Follow-up after 10 months• Complete remission
maintained; good PS• Corroborates use of
continued treatment in absence of disease progression
Case study 1 (cont’d)
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• If rash occurs, do not automatically stop Tarceva• Important to verify proper dosing and administration
Moderate SevereMild
Grade 3/4
<9% patients in BR.21 (n=731)1
12% patients in TRUST* (n=2,412)2
*Single-arm, multicentre, phase IV study of Tarceva 150mg/day in patients with advanced NSCLC who had failed or were not suitable for chemotherapy
1Shepherd FA, et al. N Engl J Med 2005;353:123–322Reck M, et al. J Clin Oncol 2006;24(Suppl. 18):411s (Abs. 7190)
Management of rash
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Consider dose reduction/interruption
Consider rash treatment strategies
From start of therapy: twice daily application of alcohol-free emollient cream to entire body, and sunscreen to exposed skin, may help prevent
skin reactions
Moderate SevereMild
Management of rash (cont’d)
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Management recommendations for symptomatic rash (assess every 2 weeks)
Hydrocortisone1–2% cream
OR
Clindamycin gel or cream, if infected
Synthetictetracycline*
AND
*Doxycycline 100mg b.i.d.†Prednisone, methylprednisolone 30mg once daily (tapered over 30 days)
Treat as moderate
Systemic steroids†
Consider dose interruption
AND
AND
Hydrocortisone1–2% cream
No treatment
OR
Moderate SevereMild
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Case study 1 (cont’d)
• Grade 3 rash occurred
• Dose reduced to 100mg after 3 weeks on therapy
• Dose reduced to 50mg after a further month
• Complete remission of rash after 4 weeks– dose increased to 100mg
• In the TRUST study of Tarceva 150mg/day (n=2,041), dose reductions due to erlotinib-related rash were necessary in only 8% of patients1
1Reck M, et al. J Clin Oncol 2006;24(Suppl. 18):411s (Abs. 7190)
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Case study 2
Case kindly provided by:
Prof Jean-Charles SoriaInstitut Gustave Roussy, Villejuif, France
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Case study 2
• 61-year-old female, Caucasian, never-smoker; PS 1
• October 2004: lung adenocarcinoma– stage T2N0M1 (IV)
• brain metastases
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Case study 2 (cont’d)
• Total brain radiotherapy (10 sessions), followed by five cycles of cisplatin + vinorelbine
• Chemotherapy discontinued due to grade 3 anorexia and deterioration in PS
• Partial response in lung and brain (March 2005)
• June 2006: progression in lung– confusion, secondary to carcinomatous leptomeningitis
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Case study 2 (cont’d)
• Patient received high-dose steroids– slight improvement
• Treatment initiated with Tarceva 150mg/day– confusion improved within 72 hours– disappearance of carcinomatous cells in cerebrospinal fluid
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Before treatment After 9 weeks of Tarceva
Case study 2 (cont’d)
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Case study 2 (cont’d)
Before treatment After 9 weeks of Tarceva
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Case study 2 (cont’d)
• December 2006: progressive disease (PD), new medullary lesions
• January 2007: confusion; increase of medullary lesions
• Tarceva 300mg/day no improvement
• Reappearance of carcinomatous cells in cerebrospinal fluid
• Rapid global status degradation
• Treatment stopped; BSC
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Small retrospective case series of EGFR TKIs in patients with brain metastases
Responders Survival (months)
n=14 6 9.1
n=57 19 13.4 (responders)
6.1 (non-responders)
Hotta K, et al. Lung Cancer 2004;46:255–61Chiu C-H, et al. Lung Cancer 2005;47:129–
38
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Ongoing studies of Tarceva in patients with brain metastases
Study Phase Treatments
RTOG-0320 Pilot Assess level of Tarceva in cerebrospinal fluid
NCT00385398 II Stereotactic radiosurgery, temozolomide, Tarceva
NCT00096265 III WBRTWBRT + stereotactic radiosurgery + temozolomideWBRT + stereotactic radiosurgery + Tarceva
NCT00268684 III WBRT + SRSWBRT + SRS + temozolomideWBRT + SRS + Tarceva
SRS = somatostatin receptor scintigraphy; WBRT = whole brain radiotherapy
Source: www.cancer.gov
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Case study 3
Case kindly provided by:
Prof Tudor-Eliade Ciuleanu
Cancer Institute Ion Chiricuta, and University of Medicine and Pharmacy Iuliu Hatieganu, Cluj-Napoca, Romania
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Case study 3
• 53-year-old female; 15 cigarettes/day for 23 years; PS 1
• Right lower lobe tumour (CT scan; 7–8cm) with carinal invasion
• Multiple enlarged mediastinal lymph nodes (1–1.5cm)
• Adenocarcinoma (bronchoscopy)– stage T4N2M0 (IIIB)
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Case study 3 (cont’d)
• Three cycles of etoposide + cisplatin, followed by RT(30 Gy/10 fractions for 12 days) SD
• PD after 4 months; tumour size 12cm; PS worsened (PS 2)
severity of cough, dyspnoea, pain, haemoptysis
• Chemotherapy discontinued
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Case study 3 (cont’d)
• Patient requested a trial with Tarceva (entered into BR.21 study)
• Tarceva 150mg/day initiated
• Cough and pain improved (grade 21); haemoptysis resolved; fatigue remained stable
• Self-rated QoL was stable, as was performance status (PS 2)
• Grade 1 stomatitis (resolved spontaneously after 2 months)
• Mild (grade 1) facial rash throughout treatment; no discomfort
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Case study 3 (cont’d)
• Best response was SD; maintained for 6 months during continuous treatment with Tarceva
• After 6 months a CT scan showed PD and Tarceva was discontinued
• 3 months later, the patient agreed to receive three cycles of docetaxel 75mg/m2 every 3 weeks SD
• Subsequently remained stable and survived >3 years after starting Tarceva
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Radiographic response to Tarceva is not required to obtain a survival benefit (BR.21)
Tarceva Placebo
nMedian survival* n
Median survival* HR p value
SD/PD 367 7.4 204 6.7 0.82 0.037
*Months
OSI Pharmaceuticals and Roche; data on file
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Key learnings
• Tumour response is not essential to benefit from Tarceva
• Tarceva has a favourable tolerability profile versus chemotherapy– rash is easily managed and does not usually affect
patients’ daily lives
• Tarceva produces important symptom and QoL benefits
• Tarceva may have a role in the treatment of patients with central nervous system metastases