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Hycamtin clinical data - Small Cell Lung Cancer

Hycamtin clinical data - Small Cell Lung Cancer. Graham Ross European Medical Affairs. Objectives. SCLC in context Randomised phase III registration trial Supporting data Key messages Literature. Lung cancer: EU figures. New cases - 42.19 per 100, 00

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Hycamtin clinical data - Small Cell Lung Cancer

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  1. Hycamtin clinical data -Small Cell Lung Cancer Graham Ross European Medical Affairs

  2. Objectives • SCLC in context • Randomised phase III registration trial • Supporting data • Key messages • Literature

  3. Lung cancer: EU figures • New cases - 42.19 per 100, 00 • Highest in Belgium and lowest in Sweden • Death rate - 38.62 per 100, 000 • Highest in Denmark and lowest in Portugual • Leading cause of death in both men and women

  4. Lung cancer: SCLC • Accounts for 20 to 25% of all lung cancer cases • Tobacco smoking is the primary risk factor • Two thirds of patients have extensive disease at time of diagnosis • Biologically aggressive disease • Median survival with LD is 12-15 weeks • Medical survival with ED is 6-9 weeks

  5. Lung cancer: Common regimes • Standard agents used in combinations • cisplatin (P), cyclophosphamide (C), doxorubicin (A), etoposide (E), vincristine (V) • CAV, EP, PE, CAVE, CEV, CAE • High response to 1st-line therapy (70-90%) • But 90% of patients relapse • Median survival of untreated relapse is 1.5 months

  6. Randomised phase III trial comparing Hycamtin with CAV in relapsed SCLC SB study 090 Von Pawel et al. JCO, 1999; 17: 658-667

  7. Randomised phase III trial 090 - Study Design Monitor Treatment Phase Topotecan 1.5 mg/m2/day x 5 (n=107) Relapse CAV* (n=104) 0 1 2 3 4 5 6 7 8 + Cycles (median = 4 for topotecan & 3 for CAV) *CAV: Cyclophosphamide 1g/m2, doxorubicin 45mg/m2 and vincristine 2 mg on day 1 every 21 days

  8. Inclusion Documented LD or ED progressing >60 days after 1st line chemo At least 1 bidimensionally measurable lesion ECOG performance status <2 Adequate renal function, bone marrow status, liver function Exclusion Symptomatic brain metastasis Cardiac disease Cumulative doxorubicin dose More than 1 prior chemotherapy Randomised phase III trial 090 - Key entry criteria

  9. Primary efficacy measure Response rate Duration of response Secondary efficacy measures Time to progression Time to response Survival Improvement in disease-related symptoms Randomised phase III trial 090 - Key efficacy measures Response rates subject to independent radiological reviews

  10. Survival Time to Progression Duration of Response Time to Response Start of treatment Response Death Progression Randomised phase III trial 090 - Efficacy endpoints

  11. Randomised phase III trial 090 - Patient demographics * Statistically significant vs Hycamtin (p=0.4)

  12. Randomised phase III trial 090 - Objective response rates 53% 46% % Patients 24%* 24% 19% 18% 17% 11% 0 1% ORR=Objective response rate CR=Complete response PR=Partial response SD=Stable disease PD=Progressive disease * Not statistically different

  13. Randomised phase III trial 090 - Additional endpoints Differences between Hycamtin and CAV were not statistically significant

  14. Randomised phase III trial 090 - Disease related symptoms

  15. Randomised phase III trial 090 - Grade 3/4 haematological side effects

  16. Randomised phase III trial 090 - Grade 3/4 non-haematological side effects: > 5% of patients

  17. Summary • Hycamtin is at least as effective in treating relapsed SCLC as the triple combination CAV • Hycamtin is well tolerated • Hycamtin is associated with improvement in disease-related symptoms

  18. Single agent phase II trial of Hycamtin in refractory or sensitive relapsed SCLC SB study 014 Ardizzoni et al. JCO, 1997; 5: 2090-2096

  19. Phase II single agent trial 014 - Design and stratification • Open label, multi-centre phase II study • Topotecan 1.5 mg/m2/day x5 days q 21 days • Sensitive - response and no disease progression for three months • Refractory - progression during prior therapy or within three months

  20. Inclusion Confirmed SCLC with progression At least one bi-dimensionally measurable lesion WHO performance status < 2 Adequate bone marrow, liver function and renal function Brain metastasis Exclusion Systemic medication within 3 weeks Life expectancy of < 3 months Phase II single agent trial 014 - Key entry criteria

  21. Phase II single agent trial 014 - Key efficacy requirements • Primary endpoint measures • WHO response rates • CTC toxicity • Secondary endpoint measures • Time to progression • Survival

  22. Phase II single agent trial 014 - Objective rates 38%* ORR 22% % Percentage Response Rate 6% * Difference in responses refractory vs sensitive p=0.008

  23. Phase II single agent trial 014 - Additional endpoints Difference in survival between sensitive and refractory patients, p<0.0027

  24. Phase II single agent trial 014 - Grade 3/4 Haematological toxicity

  25. Phase II single agent trial 014 - Grade 3/4 non-haematological toxicity

  26. Other supportive phase II studies - Studies 053 and 092

  27. Summary • Hycamtin provides durable responses (22-31 weeks) with a median survival of 22-27 weeks in patients with relapsed SCLC • Hycamtin is well tolerated

  28. Key Message 1 • Hycamtin is at least as effective as the triple combination ( CAV ) in treating patients with relapsed small cell lung cancer

  29. Key Message 2 • Hycamtin is effective in treating the disease symptoms in patients with relapsed small cell lung cancer

  30. Key Message 3 • Hycamtin is well tolerated • Adverse events are not cumulative • Non-haematological side effects are generally mild to moderate • Haematological side effects are predictable, manageable and rarely results in complex sequelae

  31. Key message 4 Ongoing Clinical Development: 1) Registration of oral Hycamtin 2) Development of 1st line combinations (cisplatin and etoposide combinations) 3) Other indications

  32. Literature • Von Pawel et al JCO, 1999; 17: 658-667 • Ardizzoni et a; JCO, 1997; 15: 2090-2096 • Von Pawel et al. JCO, 2001; 19: 1743-1749 • Depierre et al. Lung Cancer, 1997: 18 (Suppl 1): Abstract 126) • Eckardt et al. Ann Oncol, 1996;

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