A. Tfayli - Head and neck - Guidelines and clinical case presentation (2-3 ca...
LLA 2011 - J.M. Connors - Problems of the design and interpretation of phase II and III trials
1. Challenges in Interpreting Phase II and III Clinical Trial Data Joseph M Connors, MD British Columbia Cancer Agency University of British Columbia June 2011 Ascona
2. Disclosures: Joseph M Connors, MD My presentation may include discussion of off-label use of alemtuzumab bendamustine bortezomib brentuximab vedotin cisplatin cytarabine denileukin diftitox etoposide gemcitabine lenalidomide 131 I-tositumomab rituximab thalidomide 90 Y-ibritumomab June 2011 Research Support including clinical trials NCIC Canada, SWOG, Amgen, Bayer Healthcare, Cephalon, Genentech, Johnson & Johnson, Roche Canada (Hoffmann-La Roche), Lilly, Merck, Seattle Genetics Employee None Paid Consultant None Stockholder None Speakers’ Bureau None Paid Advisory Board - Pharma None Advisory Board/Committee - Foundation ASH, ASCO, Lymphoma Foundation Canada, Lymphoma Research Foundation (US), NCIC Canada Board member None
20. B Bleomycin E Etoposide A Adriamycin C Cyclophos O Vincristine P Procarbazine P Prednisone Std mg/m 2 10 100 25 650 1,4 100 40 Challenges in Interpreting Phase II and III Clinical Trials Dose Intensity Escalated mg/m 2 10 200 35 1250 1,4 100 40 G-CSF sc 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 22 restart
21. HD9 Trial Design( 1992-97 ) (1281 patients recruited) CS IIB-IIIA with risk factors CS IV Arm A 4x COPP+ABVD RT Arm B 8x BEACOPP standard RT Arm C 8x BEACOPP escalated RT+G-CSF RT to initial bulk and residual tumor
22. Engert, A. et al. J Clin Oncol; 27:4548-4554 2009 Kaplan-Meier analysis of the probability of (A) freedom from treatment failure
23. Kaplan-Meier analysis of the probability of (B) overall survival in each treatment arm Engert, A. et al. J Clin Oncol; 27:4548-4554 2009
24. Engert, JCO 2009; 27:4548 Kaplan-Meier analysis of the probability of (A) freedom from treatment failure COPP/ABVD arm closed early > 15 y ago
25. ABVD for Advanced Stage Hodgkin Lymphoma ~ 90 % 5-y OS % Year of publication First author 73 1992 Canellos 78 1998 Hasenclever 82 2003 Duggan 83 2003 Diehl 86 2008 Gianni 84 2009 Federico 90 2009 Hoskin 91 2009 Moccia 88 2010 Gordon
26. SV after relapse (months) Probability Survival after relapse Arm C 10 / 22 (5%) Arm B 19 / 42 (8%) Arm A 11 / 37 (15%) GHSG 2001 HD9 A vs. B : p=0.033 A vs. C : p=0.105 B vs. C : p=0.893 BEACOPP esc. BEACOPP bas. COPP/ABVD 100 80 60 40 20 0 1,0 ,8 ,6 ,4 ,2 0,0
53. Demographics and Baseline Characteristics N=102 Age* 31 yr (15 77) Gender 48 M / 54 F ECOG status 0 42 (41%) 1 60 (59%) Refractory to frontline therapy 72 (71%) Refractory to most recent treatment 43 (42%) Prior chemotherapy regimens* 3.5 (1 13) Prior radiation 67 (66%) Prior ASCT 102 (100%) Time from ASCT to first post transplant relapse* 6.7 mo (0 131) * Median (range)
Kaplan-Meier analysis of the probability of the failure-free survival, progression-free survival, relapse-free survival, and overall survival according to intention to treat. ABVD, doxorubicin, bleomycin, vinblastine, and dacarbazine; BEA, bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone; CEC, cyclophosphamide, vincristine, procarbazine, prednisone, epidoxirubicin, bleomycin, vinblastine, lomustine, doxorubicin, and vindesine.