HeinsHansen.ppt

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HeinsHansen.ppt

  1. 1. Second-line treatment in action Heine Hansen National University Hospital, Copenhagen, Denmark
  2. 2. Case study 1 Case kindly provided by: Dr Wolfgang Schütte Städtisches Krankenhaus Martha-Maria Halle Dölau, Germany
  3. 3. 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
  4. 4. 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?
  5. 5. 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)
  6. 6. • 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 1 Shepherd FA, et al. N Engl J Med 2005;353:123–32 2 Reck M, et al. J Clin Oncol 2006;24(Suppl. 18):411s (Abs. 7190) Management of rash
  7. 7. 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)
  8. 8. Management recommendations for symptomatic rash (assess every 2 weeks) Hydrocortisone 1–2% cream OR Clindamycin gel or cream, if infected Synthetic tetracycline* 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 Hydrocortisone 1–2% cream No treatment OR Moderate SevereMild
  9. 9. 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 1 Reck M, et al. J Clin Oncol 2006;24(Suppl. 18):411s (Abs. 7190)
  10. 10. Case study 2 Case kindly provided by: Prof Jean-Charles Soria Institut Gustave Roussy, Villejuif, France
  11. 11. Case study 2 • 61-year-old female, Caucasian, never-smoker; PS 1 • October 2004: lung adenocarcinoma – stage T2N0M1 (IV) • brain metastases
  12. 12. 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
  13. 13. 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
  14. 14. Before treatment After 9 weeks of Tarceva Case study 2 (cont’d)
  15. 15. Case study 2 (cont’d) Before treatment After 9 weeks of Tarceva
  16. 16. 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
  17. 17. 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;46:255–61 Chiu C-H, et al. Lung Cancer 2005;47:129– 38
  18. 18. 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 WBRT WBRT + stereotactic radiosurgery + temozolomide WBRT + stereotactic radiosurgery + Tarceva NCT00268684 III WBRT + SRS WBRT + SRS + temozolomide WBRT + SRS + Tarceva SRS = somatostatin receptor scintigraphy; WBRT = whole brain radiotherapy Source: www.cancer.gov
  19. 19. 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
  20. 20. 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)
  21. 21. 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
  22. 22. 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 2→1); 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
  23. 23. 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
  24. 24. Radiographic response to Tarceva is not required to obtain a survival benefit (BR.21) Tarceva Placebo n Median 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
  25. 25. 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

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