SlideShare ist ein Scribd-Unternehmen logo
1 von 55
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
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
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Challenges in Interpreting Phase II and III Clinical Trials
[object Object],[object Object],Challenges in Interpreting Phase II and III Clinical Trials Generalizability
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Challenges in Interpreting Phase II and III Clinical Trials Generalizability
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Challenges in Interpreting Phase II and III Clinical Trials Generalizability ,[object Object],18%
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Challenges in Interpreting Phase II and III Clinical Trials Generalizability
[object Object],[object Object],[object Object],[object Object],[object Object],Challenges in Interpreting Phase II and III Clinical Trials Generalizability
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Challenges in Interpreting Phase II and III Clinical Trials Generalizability
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Challenges in Interpreting Phase II and III Clinical Trials Generalizability
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Challenges in Interpreting Phase II and III Clinical Trials Generalizability
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Challenges in Interpreting Phase II and III Clinical Trials Generalizability ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],Challenges in Interpreting Phase II and III Clinical Trials Treatment Intensity
[object Object],[object Object],[object Object],[object Object],Challenges in Interpreting Phase II and III Clinical Trials Dose Intensity
[object Object],[object Object],[object Object],[object Object],Challenges in Interpreting Phase II and III Clinical Trials Treatment Intensity ,[object Object],[object Object],[object Object]
Challenges in Interpreting Phase II and III Clinical Trials Treatment Intensity ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Challenges in Interpreting Phase II and III Clinical Trials Treatment Intensity
[object Object],[object Object],Challenges in Interpreting Phase II and III Clinical Trials Dose Intensity ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Challenges in Interpreting Phase II and III Clinical Trials Dose Intensity
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
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
Engert, A. et al. J Clin Oncol; 27:4548-4554 2009 Kaplan-Meier analysis of the probability of (A) freedom from treatment failure
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
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
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
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
Cure esc BEACOPP Potential Strategies to Cure Advanced Stage Hodgkin Lymphoma ABVD High dose chemotherapy + autologous stem cell transplant Progression Endpoints = PFS  RFS EFS  TTP Endpoints = OS FF2F Progression Cure
Potential Strategies to Cure Advanced Stage Hodgkin Lymphoma Study Regimen 5-y PFS (%) P 5-y OS (%) P Reference GHSG HD9 eBEACOPP 87 0.001 91 0.02 Diehl, 2003 COPP/ABVD 69 83 GISL HD2000 eBEACOPP 81 0.038 92 NS Federico, 2009 ABVD 68 84 GSM-HD eBEACOPP 85 0.004 89 0.39 Gianni, 2008 ABVD 73 86
Kaplan-Meier analysis of the probability of the progression-free survival and overall survival according to intention to treat. Federico M et al. JCO 2009;27:805-811 ©2009 by American Society of Clinical Oncology Endpoint = PFS Endpoint = OS
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Challenges in Interpreting Phase II and III Clinical Trials Treatment Intensity
[object Object],[object Object],Challenges in Interpreting Phase II and III Clinical Trials Stage Migration & Lead Time Bias
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Challenges in Interpreting Phase II and III Clinical Trials Stage Migration & Lead Time Bias
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Challenges in Interpreting Phase II and III Clinical Trials Stage Migration & Lead Time Bias Treatment must have become more effective
Challenges in Interpreting Phase II and III Clinical Trials Stage Migration & Lead Time Bias
Lead time bias Challenges in Interpreting Phase II and III Clinical Trials Stage Migration & Lead Time Bias
Correction for lead time bias Challenges in Interpreting Phase II and III Clinical Trials Stage Migration & Lead Time Bias
Impact of new tests on the 131 Era 2 (1977) patients Challenges in Interpreting Phase II and III Clinical Trials Stage Migration & Lead Time Bias
Challenges in Interpreting Phase II and III Clinical Trials Stage Migration & Lead Time Bias
Challenges in Interpreting Phase II and III Clinical Trials Stage Migration & Lead Time Bias x
Correction for lead time bias Challenges in Interpreting Phase II and III Clinical Trials Stage Migration & Lead Time Bias
Hodgkin lymphoma  Treatment by Stage ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Hodgkin Lymphoma  Staging ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Lymphoma: FDG/PET/CT ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
 
Lymphoma: FDG/PET/CT ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Challenges in Interpreting Phase II and III Clinical Trials Stage Migration & Lead Time Bias
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Challenges in Interpreting Phase II and III Clinical Trials
Hodgkin Lymphoma  Limited Stage ,[object Object],[object Object],[object Object],[object Object],[object Object]
Hodgkin Lymphoma  Limited Stage ,[object Object],[object Object],[object Object],[object Object],[object Object],ABVD x 2   PET   PET neg   PET pos   ABVD x 2   IFRT   n = 117 117 117 96  (82 %) 21  (18 %) 95 22 Relapse   4 2 Deaths   Hodg 0 0 (BMT)   (3) (2) Feb 2011
Feb 2011
Feb 2011
 
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)
Maximum Tumor Reduction per IRF ,[object Object],[object Object],[object Object],Individual Patients (n=98)* Tumor Size (% Change from Baseline) 94% (96 of 102) of patients achieved tumor reduction 100
Response Results N=102 IRF Investigator Overall response rate (95% CI) 75% (65, 83) 72% (62, 80) Complete remission  34% 33% Partial remission 40% 38% Stable disease 22% 27% Progressive disease 3% 0% Not evaluable 1% 1%

Weitere ähnliche Inhalte

Was ist angesagt?

Targeted therapy for Hodgkin’s Lymphoma
Targeted therapy for Hodgkin’s LymphomaTargeted therapy for Hodgkin’s Lymphoma
Targeted therapy for Hodgkin’s Lymphomaspa718
 
(Ohio State's 2016 ASH Review) ASH 2015 REVIEW – LYMPHOMA ABSTRACTS
(Ohio State's 2016 ASH Review) ASH 2015 REVIEW – LYMPHOMA ABSTRACTS(Ohio State's 2016 ASH Review) ASH 2015 REVIEW – LYMPHOMA ABSTRACTS
(Ohio State's 2016 ASH Review) ASH 2015 REVIEW – LYMPHOMA ABSTRACTSOSUCCC - James
 
Follicular Lymphoma: Applying Emerging Evidence in Practice
Follicular Lymphoma: Applying Emerging Evidence in PracticeFollicular Lymphoma: Applying Emerging Evidence in Practice
Follicular Lymphoma: Applying Emerging Evidence in PracticeChristi C.
 
Immunotherapy for lymphoma
Immunotherapy  for lymphomaImmunotherapy  for lymphoma
Immunotherapy for lymphomaChandan K Das
 
6 frederick
6 frederick6 frederick
6 frederickspa718
 
Clinical Trials, Emerging New Drugs and Future Concepts in the Treatment of L...
Clinical Trials, Emerging New Drugs and Future Concepts in the Treatment of L...Clinical Trials, Emerging New Drugs and Future Concepts in the Treatment of L...
Clinical Trials, Emerging New Drugs and Future Concepts in the Treatment of L...Dana-Farber Cancer Institute
 
ASCO 2014 update in GI cancer
ASCO 2014 update in GI cancer ASCO 2014 update in GI cancer
ASCO 2014 update in GI cancer spa718
 
Ohio State's 2016 ASH Review - ASH Review 2015 Acute Leukemias and MDS
Ohio State's 2016 ASH Review - ASH Review 2015Acute Leukemias and MDSOhio State's 2016 ASH Review - ASH Review 2015Acute Leukemias and MDS
Ohio State's 2016 ASH Review - ASH Review 2015 Acute Leukemias and MDSOSUCCC - James
 
Ohio State's 2016 ASH Review T-cell Disorders
Ohio State's 2016 ASH Review T-cell DisordersOhio State's 2016 ASH Review T-cell Disorders
Ohio State's 2016 ASH Review T-cell DisordersOSUCCC - James
 
Tumor board
Tumor boardTumor board
Tumor boardmadurai
 
Ohio State's 2016 ASH Review Blood and Marrow Trasplantation (with Turning Po...
Ohio State's 2016 ASH Review Blood and Marrow Trasplantation (with Turning Po...Ohio State's 2016 ASH Review Blood and Marrow Trasplantation (with Turning Po...
Ohio State's 2016 ASH Review Blood and Marrow Trasplantation (with Turning Po...OSUCCC - James
 
Advances for Non Small cell Lung Cancer
Advances for Non Small cell Lung CancerAdvances for Non Small cell Lung Cancer
Advances for Non Small cell Lung Cancerspa718
 
Role of Apalutamide in management of M0 CRPC
Role of Apalutamide in management of M0 CRPCRole of Apalutamide in management of M0 CRPC
Role of Apalutamide in management of M0 CRPCMohamed Abdulla
 
Hepatobiliary tumor board (1)
Hepatobiliary tumor board (1)Hepatobiliary tumor board (1)
Hepatobiliary tumor board (1)madurai
 
Gene Profiling in Clinical Oncology - Slide 6 - A. Sobrero - Is T4, fewer tha...
Gene Profiling in Clinical Oncology - Slide 6 - A. Sobrero - Is T4, fewer tha...Gene Profiling in Clinical Oncology - Slide 6 - A. Sobrero - Is T4, fewer tha...
Gene Profiling in Clinical Oncology - Slide 6 - A. Sobrero - Is T4, fewer tha...European School of Oncology
 
evolving role of anti angiogenesis in metastatic crc
evolving role of anti angiogenesis in metastatic crcevolving role of anti angiogenesis in metastatic crc
evolving role of anti angiogenesis in metastatic crcMohamed Abdulla
 
Breast cancer quiz (For Radiation Oncology residents)
Breast cancer quiz (For Radiation Oncology residents)Breast cancer quiz (For Radiation Oncology residents)
Breast cancer quiz (For Radiation Oncology residents)Bharti Devnani
 
AML and Cell Therapy
AML and Cell TherapyAML and Cell Therapy
AML and Cell Therapyspa718
 

Was ist angesagt? (18)

Targeted therapy for Hodgkin’s Lymphoma
Targeted therapy for Hodgkin’s LymphomaTargeted therapy for Hodgkin’s Lymphoma
Targeted therapy for Hodgkin’s Lymphoma
 
(Ohio State's 2016 ASH Review) ASH 2015 REVIEW – LYMPHOMA ABSTRACTS
(Ohio State's 2016 ASH Review) ASH 2015 REVIEW – LYMPHOMA ABSTRACTS(Ohio State's 2016 ASH Review) ASH 2015 REVIEW – LYMPHOMA ABSTRACTS
(Ohio State's 2016 ASH Review) ASH 2015 REVIEW – LYMPHOMA ABSTRACTS
 
Follicular Lymphoma: Applying Emerging Evidence in Practice
Follicular Lymphoma: Applying Emerging Evidence in PracticeFollicular Lymphoma: Applying Emerging Evidence in Practice
Follicular Lymphoma: Applying Emerging Evidence in Practice
 
Immunotherapy for lymphoma
Immunotherapy  for lymphomaImmunotherapy  for lymphoma
Immunotherapy for lymphoma
 
6 frederick
6 frederick6 frederick
6 frederick
 
Clinical Trials, Emerging New Drugs and Future Concepts in the Treatment of L...
Clinical Trials, Emerging New Drugs and Future Concepts in the Treatment of L...Clinical Trials, Emerging New Drugs and Future Concepts in the Treatment of L...
Clinical Trials, Emerging New Drugs and Future Concepts in the Treatment of L...
 
ASCO 2014 update in GI cancer
ASCO 2014 update in GI cancer ASCO 2014 update in GI cancer
ASCO 2014 update in GI cancer
 
Ohio State's 2016 ASH Review - ASH Review 2015 Acute Leukemias and MDS
Ohio State's 2016 ASH Review - ASH Review 2015Acute Leukemias and MDSOhio State's 2016 ASH Review - ASH Review 2015Acute Leukemias and MDS
Ohio State's 2016 ASH Review - ASH Review 2015 Acute Leukemias and MDS
 
Ohio State's 2016 ASH Review T-cell Disorders
Ohio State's 2016 ASH Review T-cell DisordersOhio State's 2016 ASH Review T-cell Disorders
Ohio State's 2016 ASH Review T-cell Disorders
 
Tumor board
Tumor boardTumor board
Tumor board
 
Ohio State's 2016 ASH Review Blood and Marrow Trasplantation (with Turning Po...
Ohio State's 2016 ASH Review Blood and Marrow Trasplantation (with Turning Po...Ohio State's 2016 ASH Review Blood and Marrow Trasplantation (with Turning Po...
Ohio State's 2016 ASH Review Blood and Marrow Trasplantation (with Turning Po...
 
Advances for Non Small cell Lung Cancer
Advances for Non Small cell Lung CancerAdvances for Non Small cell Lung Cancer
Advances for Non Small cell Lung Cancer
 
Role of Apalutamide in management of M0 CRPC
Role of Apalutamide in management of M0 CRPCRole of Apalutamide in management of M0 CRPC
Role of Apalutamide in management of M0 CRPC
 
Hepatobiliary tumor board (1)
Hepatobiliary tumor board (1)Hepatobiliary tumor board (1)
Hepatobiliary tumor board (1)
 
Gene Profiling in Clinical Oncology - Slide 6 - A. Sobrero - Is T4, fewer tha...
Gene Profiling in Clinical Oncology - Slide 6 - A. Sobrero - Is T4, fewer tha...Gene Profiling in Clinical Oncology - Slide 6 - A. Sobrero - Is T4, fewer tha...
Gene Profiling in Clinical Oncology - Slide 6 - A. Sobrero - Is T4, fewer tha...
 
evolving role of anti angiogenesis in metastatic crc
evolving role of anti angiogenesis in metastatic crcevolving role of anti angiogenesis in metastatic crc
evolving role of anti angiogenesis in metastatic crc
 
Breast cancer quiz (For Radiation Oncology residents)
Breast cancer quiz (For Radiation Oncology residents)Breast cancer quiz (For Radiation Oncology residents)
Breast cancer quiz (For Radiation Oncology residents)
 
AML and Cell Therapy
AML and Cell TherapyAML and Cell Therapy
AML and Cell Therapy
 

Ähnlich wie LLA 2011 - J.M. Connors - Problems of the design and interpretation of phase II and III trials

Hodgkin’S And Non Hodgkin’S Lymphoma
Hodgkin’S And Non Hodgkin’S LymphomaHodgkin’S And Non Hodgkin’S Lymphoma
Hodgkin’S And Non Hodgkin’S Lymphomafondas vakalis
 
colon cancer synopsis 2015
colon cancer synopsis 2015colon cancer synopsis 2015
colon cancer synopsis 2015Mohamed Abdulla
 
ECCLU 2011 - K. Fizazi - Testicular cancer - Treatment of advanced testicular...
ECCLU 2011 - K. Fizazi - Testicular cancer - Treatment of advanced testicular...ECCLU 2011 - K. Fizazi - Testicular cancer - Treatment of advanced testicular...
ECCLU 2011 - K. Fizazi - Testicular cancer - Treatment of advanced testicular...European School of Oncology
 
02 ptcl ylk
02 ptcl  ylk02 ptcl  ylk
02 ptcl ylkspa718
 
The Role of Radiotherapy in the Treatment of Early Stage Ocular Marginal Zone...
The Role of Radiotherapy in the Treatment of Early Stage Ocular Marginal Zone...The Role of Radiotherapy in the Treatment of Early Stage Ocular Marginal Zone...
The Role of Radiotherapy in the Treatment of Early Stage Ocular Marginal Zone...daranisaha
 
Potential of phase II clinical trials in drug development
Potential of phase II clinical trials in drug developmentPotential of phase II clinical trials in drug development
Potential of phase II clinical trials in drug developmentBhaswat Chakraborty
 
BALKAN MCO 2011 - S. Beslija - Controversies in recurrent ovarian cancer: rol...
BALKAN MCO 2011 - S. Beslija - Controversies in recurrent ovarian cancer: rol...BALKAN MCO 2011 - S. Beslija - Controversies in recurrent ovarian cancer: rol...
BALKAN MCO 2011 - S. Beslija - Controversies in recurrent ovarian cancer: rol...European School of Oncology
 
Management of colorectal cancer
Management of colorectal cancer Management of colorectal cancer
Management of colorectal cancer Mohamed Abdulla
 
Hodgkin Lymphoma: Latest Concepts
Hodgkin Lymphoma: Latest ConceptsHodgkin Lymphoma: Latest Concepts
Hodgkin Lymphoma: Latest Conceptsspa718
 
ECCLU 2011 - N. James - Localised invasive bladder cancer - Radiotherapy
ECCLU 2011 - N. James - Localised invasive bladder cancer - RadiotherapyECCLU 2011 - N. James - Localised invasive bladder cancer - Radiotherapy
ECCLU 2011 - N. James - Localised invasive bladder cancer - RadiotherapyEuropean School of Oncology
 
Cholangiocarcinoma
CholangiocarcinomaCholangiocarcinoma
Cholangiocarcinomaspa718
 
Evolving Role of Radiation Therapy in Hodgkins Disease
Evolving Role of Radiation Therapy in Hodgkins DiseaseEvolving Role of Radiation Therapy in Hodgkins Disease
Evolving Role of Radiation Therapy in Hodgkins DiseaseSantam Chakraborty
 
V_Hematology_Forum_Mikhailova_NB_02
V_Hematology_Forum_Mikhailova_NB_02V_Hematology_Forum_Mikhailova_NB_02
V_Hematology_Forum_Mikhailova_NB_02EAFO1
 
C:\Documents And Settings\User\Desktop\Head And Neck
C:\Documents And Settings\User\Desktop\Head And NeckC:\Documents And Settings\User\Desktop\Head And Neck
C:\Documents And Settings\User\Desktop\Head And NeckGamal Abdul Hamid
 
Advances In Adjuvant Systemic Therapy Of Breast Cancer
Advances In Adjuvant Systemic Therapy Of Breast CancerAdvances In Adjuvant Systemic Therapy Of Breast Cancer
Advances In Adjuvant Systemic Therapy Of Breast Cancerfondas vakalis
 
Adjuvant systemic therapy in resectable non-small cell lung cancer, Moh'd sha...
Adjuvant systemic therapy in resectable non-small cell lung cancer, Moh'd sha...Adjuvant systemic therapy in resectable non-small cell lung cancer, Moh'd sha...
Adjuvant systemic therapy in resectable non-small cell lung cancer, Moh'd sha...Moh'd sharshir
 
Medical Students 2011 - J.B. Vermorken - GYNAECOLOGICAL CANCER SESSION - Epit...
Medical Students 2011 - J.B. Vermorken - GYNAECOLOGICAL CANCER SESSION - Epit...Medical Students 2011 - J.B. Vermorken - GYNAECOLOGICAL CANCER SESSION - Epit...
Medical Students 2011 - J.B. Vermorken - GYNAECOLOGICAL CANCER SESSION - Epit...European School of Oncology
 
Mantle Cell Lymphoma: from bench to clinic
Mantle Cell Lymphoma: from bench to clinicMantle Cell Lymphoma: from bench to clinic
Mantle Cell Lymphoma: from bench to clinicspa718
 
Targeted therapy for Hodgkin’s Lymphoma
Targeted therapy for Hodgkin’s LymphomaTargeted therapy for Hodgkin’s Lymphoma
Targeted therapy for Hodgkin’s Lymphomaspa718
 

Ähnlich wie LLA 2011 - J.M. Connors - Problems of the design and interpretation of phase II and III trials (20)

Hodgkin’S And Non Hodgkin’S Lymphoma
Hodgkin’S And Non Hodgkin’S LymphomaHodgkin’S And Non Hodgkin’S Lymphoma
Hodgkin’S And Non Hodgkin’S Lymphoma
 
colon cancer synopsis 2015
colon cancer synopsis 2015colon cancer synopsis 2015
colon cancer synopsis 2015
 
ECCLU 2011 - K. Fizazi - Testicular cancer - Treatment of advanced testicular...
ECCLU 2011 - K. Fizazi - Testicular cancer - Treatment of advanced testicular...ECCLU 2011 - K. Fizazi - Testicular cancer - Treatment of advanced testicular...
ECCLU 2011 - K. Fizazi - Testicular cancer - Treatment of advanced testicular...
 
02 ptcl ylk
02 ptcl  ylk02 ptcl  ylk
02 ptcl ylk
 
The Role of Radiotherapy in the Treatment of Early Stage Ocular Marginal Zone...
The Role of Radiotherapy in the Treatment of Early Stage Ocular Marginal Zone...The Role of Radiotherapy in the Treatment of Early Stage Ocular Marginal Zone...
The Role of Radiotherapy in the Treatment of Early Stage Ocular Marginal Zone...
 
Potential of phase II clinical trials in drug development
Potential of phase II clinical trials in drug developmentPotential of phase II clinical trials in drug development
Potential of phase II clinical trials in drug development
 
BALKAN MCO 2011 - S. Beslija - Controversies in recurrent ovarian cancer: rol...
BALKAN MCO 2011 - S. Beslija - Controversies in recurrent ovarian cancer: rol...BALKAN MCO 2011 - S. Beslija - Controversies in recurrent ovarian cancer: rol...
BALKAN MCO 2011 - S. Beslija - Controversies in recurrent ovarian cancer: rol...
 
Management of colorectal cancer
Management of colorectal cancer Management of colorectal cancer
Management of colorectal cancer
 
Hodgkin Lymphoma: Latest Concepts
Hodgkin Lymphoma: Latest ConceptsHodgkin Lymphoma: Latest Concepts
Hodgkin Lymphoma: Latest Concepts
 
ECCLU 2011 - N. James - Localised invasive bladder cancer - Radiotherapy
ECCLU 2011 - N. James - Localised invasive bladder cancer - RadiotherapyECCLU 2011 - N. James - Localised invasive bladder cancer - Radiotherapy
ECCLU 2011 - N. James - Localised invasive bladder cancer - Radiotherapy
 
Cholangiocarcinoma
CholangiocarcinomaCholangiocarcinoma
Cholangiocarcinoma
 
Evolving Role of Radiation Therapy in Hodgkins Disease
Evolving Role of Radiation Therapy in Hodgkins DiseaseEvolving Role of Radiation Therapy in Hodgkins Disease
Evolving Role of Radiation Therapy in Hodgkins Disease
 
V_Hematology_Forum_Mikhailova_NB_02
V_Hematology_Forum_Mikhailova_NB_02V_Hematology_Forum_Mikhailova_NB_02
V_Hematology_Forum_Mikhailova_NB_02
 
C:\Documents And Settings\User\Desktop\Head And Neck
C:\Documents And Settings\User\Desktop\Head And NeckC:\Documents And Settings\User\Desktop\Head And Neck
C:\Documents And Settings\User\Desktop\Head And Neck
 
Asco-cim.linfoma.pptx
Asco-cim.linfoma.pptxAsco-cim.linfoma.pptx
Asco-cim.linfoma.pptx
 
Advances In Adjuvant Systemic Therapy Of Breast Cancer
Advances In Adjuvant Systemic Therapy Of Breast CancerAdvances In Adjuvant Systemic Therapy Of Breast Cancer
Advances In Adjuvant Systemic Therapy Of Breast Cancer
 
Adjuvant systemic therapy in resectable non-small cell lung cancer, Moh'd sha...
Adjuvant systemic therapy in resectable non-small cell lung cancer, Moh'd sha...Adjuvant systemic therapy in resectable non-small cell lung cancer, Moh'd sha...
Adjuvant systemic therapy in resectable non-small cell lung cancer, Moh'd sha...
 
Medical Students 2011 - J.B. Vermorken - GYNAECOLOGICAL CANCER SESSION - Epit...
Medical Students 2011 - J.B. Vermorken - GYNAECOLOGICAL CANCER SESSION - Epit...Medical Students 2011 - J.B. Vermorken - GYNAECOLOGICAL CANCER SESSION - Epit...
Medical Students 2011 - J.B. Vermorken - GYNAECOLOGICAL CANCER SESSION - Epit...
 
Mantle Cell Lymphoma: from bench to clinic
Mantle Cell Lymphoma: from bench to clinicMantle Cell Lymphoma: from bench to clinic
Mantle Cell Lymphoma: from bench to clinic
 
Targeted therapy for Hodgkin’s Lymphoma
Targeted therapy for Hodgkin’s LymphomaTargeted therapy for Hodgkin’s Lymphoma
Targeted therapy for Hodgkin’s Lymphoma
 

Mehr von European School of Oncology

ABC1 - X. Zhang - Metastasis seed pre-selection driven by the microenvironmen...
ABC1 - X. Zhang - Metastasis seed pre-selection driven by the microenvironmen...ABC1 - X. Zhang - Metastasis seed pre-selection driven by the microenvironmen...
ABC1 - X. Zhang - Metastasis seed pre-selection driven by the microenvironmen...European School of Oncology
 
G. Ceresoli - Prostate and renal cancer - State of the art and update on syst...
G. Ceresoli - Prostate and renal cancer - State of the art and update on syst...G. Ceresoli - Prostate and renal cancer - State of the art and update on syst...
G. Ceresoli - Prostate and renal cancer - State of the art and update on syst...European School of Oncology
 
A. Shamseddine - Prostate and renal cancer - State of the art and update on s...
A. Shamseddine - Prostate and renal cancer - State of the art and update on s...A. Shamseddine - Prostate and renal cancer - State of the art and update on s...
A. Shamseddine - Prostate and renal cancer - State of the art and update on s...European School of Oncology
 
A. Stathis - New drugs in the treatment of lymphomas
A. Stathis - New drugs in the treatment of lymphomasA. Stathis - New drugs in the treatment of lymphomas
A. Stathis - New drugs in the treatment of lymphomasEuropean School of Oncology
 
A. Stathis - Lymphomas - New drugs in the treatment of lymphomas
A. Stathis - Lymphomas - New drugs in the treatment of lymphomasA. Stathis - Lymphomas - New drugs in the treatment of lymphomas
A. Stathis - Lymphomas - New drugs in the treatment of lymphomasEuropean School of Oncology
 
S. Khleif - Ovarian cancer - General lecture on vaccine
S. Khleif - Ovarian cancer - General lecture on vaccineS. Khleif - Ovarian cancer - General lecture on vaccine
S. Khleif - Ovarian cancer - General lecture on vaccineEuropean School of Oncology
 
A. Hassan - Ovarian cancer - Guidelines and clinical case presentation (2-3 c...
A. Hassan - Ovarian cancer - Guidelines and clinical case presentation (2-3 c...A. Hassan - Ovarian cancer - Guidelines and clinical case presentation (2-3 c...
A. Hassan - Ovarian cancer - Guidelines and clinical case presentation (2-3 c...European School of Oncology
 
J.B. Vermorken - Ovarian cancer - State of the art
J.B. Vermorken - Ovarian cancer - State of the artJ.B. Vermorken - Ovarian cancer - State of the art
J.B. Vermorken - Ovarian cancer - State of the artEuropean School of Oncology
 
A. Hassan - Cervical cancer - Guidelines and clinical case presentation (2-3 ...
A. Hassan - Cervical cancer - Guidelines and clinical case presentation (2-3 ...A. Hassan - Cervical cancer - Guidelines and clinical case presentation (2-3 ...
A. Hassan - Cervical cancer - Guidelines and clinical case presentation (2-3 ...European School of Oncology
 
T. Cufer - Breast cancer - State of the art for advanced breast cancer
T. Cufer - Breast cancer - State of the art for advanced breast cancer T. Cufer - Breast cancer - State of the art for advanced breast cancer
T. Cufer - Breast cancer - State of the art for advanced breast cancer European School of Oncology
 
N. El Saghir - Breast cancer - State of the art for early breast cancer
N. El Saghir - Breast cancer - State of the art for early breast cancerN. El Saghir - Breast cancer - State of the art for early breast cancer
N. El Saghir - Breast cancer - State of the art for early breast cancerEuropean School of Oncology
 
S. Cascinu - Liver/Hepatobiliary - State of the art
S. Cascinu - Liver/Hepatobiliary - State of the artS. Cascinu - Liver/Hepatobiliary - State of the art
S. Cascinu - Liver/Hepatobiliary - State of the artEuropean School of Oncology
 
S. Cascinu - Colorectal cancer - Guidelines and clinical case presentation (2...
S. Cascinu - Colorectal cancer - Guidelines and clinical case presentation (2...S. Cascinu - Colorectal cancer - Guidelines and clinical case presentation (2...
S. Cascinu - Colorectal cancer - Guidelines and clinical case presentation (2...European School of Oncology
 
G. Pentheroudakis - Colorectal cancer - State of the art
G. Pentheroudakis - Colorectal cancer - State of the artG. Pentheroudakis - Colorectal cancer - State of the art
G. Pentheroudakis - Colorectal cancer - State of the artEuropean School of Oncology
 
A. Tfayli - Head and neck - Guidelines and clinical case presentation (2-3 ca...
A. Tfayli - Head and neck - Guidelines and clinical case presentation (2-3 ca...A. Tfayli - Head and neck - Guidelines and clinical case presentation (2-3 ca...
A. Tfayli - Head and neck - Guidelines and clinical case presentation (2-3 ca...European School of Oncology
 

Mehr von European School of Oncology (20)

ABC1 - X. Zhang - Metastasis seed pre-selection driven by the microenvironmen...
ABC1 - X. Zhang - Metastasis seed pre-selection driven by the microenvironmen...ABC1 - X. Zhang - Metastasis seed pre-selection driven by the microenvironmen...
ABC1 - X. Zhang - Metastasis seed pre-selection driven by the microenvironmen...
 
G. Ceresoli - Prostate and renal cancer - State of the art and update on syst...
G. Ceresoli - Prostate and renal cancer - State of the art and update on syst...G. Ceresoli - Prostate and renal cancer - State of the art and update on syst...
G. Ceresoli - Prostate and renal cancer - State of the art and update on syst...
 
A. Shamseddine - Prostate and renal cancer - State of the art and update on s...
A. Shamseddine - Prostate and renal cancer - State of the art and update on s...A. Shamseddine - Prostate and renal cancer - State of the art and update on s...
A. Shamseddine - Prostate and renal cancer - State of the art and update on s...
 
W. Hassen - Bladder cancer - Guidelines
W. Hassen - Bladder cancer - GuidelinesW. Hassen - Bladder cancer - Guidelines
W. Hassen - Bladder cancer - Guidelines
 
A. Stathis - New drugs in the treatment of lymphomas
A. Stathis - New drugs in the treatment of lymphomasA. Stathis - New drugs in the treatment of lymphomas
A. Stathis - New drugs in the treatment of lymphomas
 
H. Khaled - Bladder cancer - State of the art
H. Khaled - Bladder cancer - State of the artH. Khaled - Bladder cancer - State of the art
H. Khaled - Bladder cancer - State of the art
 
A. Stathis - Lymphomas - New drugs in the treatment of lymphomas
A. Stathis - Lymphomas - New drugs in the treatment of lymphomasA. Stathis - Lymphomas - New drugs in the treatment of lymphomas
A. Stathis - Lymphomas - New drugs in the treatment of lymphomas
 
1 azim
1 azim1 azim
1 azim
 
H. Azim - Lymphomas - State of the art
H. Azim - Lymphomas - State of the artH. Azim - Lymphomas - State of the art
H. Azim - Lymphomas - State of the art
 
S. Khleif - Ovarian cancer - General lecture on vaccine
S. Khleif - Ovarian cancer - General lecture on vaccineS. Khleif - Ovarian cancer - General lecture on vaccine
S. Khleif - Ovarian cancer - General lecture on vaccine
 
A. Hassan - Ovarian cancer - Guidelines and clinical case presentation (2-3 c...
A. Hassan - Ovarian cancer - Guidelines and clinical case presentation (2-3 c...A. Hassan - Ovarian cancer - Guidelines and clinical case presentation (2-3 c...
A. Hassan - Ovarian cancer - Guidelines and clinical case presentation (2-3 c...
 
J.B. Vermorken - Ovarian cancer - State of the art
J.B. Vermorken - Ovarian cancer - State of the artJ.B. Vermorken - Ovarian cancer - State of the art
J.B. Vermorken - Ovarian cancer - State of the art
 
A. Hassan - Cervical cancer - Guidelines and clinical case presentation (2-3 ...
A. Hassan - Cervical cancer - Guidelines and clinical case presentation (2-3 ...A. Hassan - Cervical cancer - Guidelines and clinical case presentation (2-3 ...
A. Hassan - Cervical cancer - Guidelines and clinical case presentation (2-3 ...
 
V. Kesic - Cervical cancer - State of the art
V. Kesic - Cervical cancer - State of the art V. Kesic - Cervical cancer - State of the art
V. Kesic - Cervical cancer - State of the art
 
T. Cufer - Breast cancer - State of the art for advanced breast cancer
T. Cufer - Breast cancer - State of the art for advanced breast cancer T. Cufer - Breast cancer - State of the art for advanced breast cancer
T. Cufer - Breast cancer - State of the art for advanced breast cancer
 
N. El Saghir - Breast cancer - State of the art for early breast cancer
N. El Saghir - Breast cancer - State of the art for early breast cancerN. El Saghir - Breast cancer - State of the art for early breast cancer
N. El Saghir - Breast cancer - State of the art for early breast cancer
 
S. Cascinu - Liver/Hepatobiliary - State of the art
S. Cascinu - Liver/Hepatobiliary - State of the artS. Cascinu - Liver/Hepatobiliary - State of the art
S. Cascinu - Liver/Hepatobiliary - State of the art
 
S. Cascinu - Colorectal cancer - Guidelines and clinical case presentation (2...
S. Cascinu - Colorectal cancer - Guidelines and clinical case presentation (2...S. Cascinu - Colorectal cancer - Guidelines and clinical case presentation (2...
S. Cascinu - Colorectal cancer - Guidelines and clinical case presentation (2...
 
G. Pentheroudakis - Colorectal cancer - State of the art
G. Pentheroudakis - Colorectal cancer - State of the artG. Pentheroudakis - Colorectal cancer - State of the art
G. Pentheroudakis - Colorectal cancer - State of the art
 
A. Tfayli - Head and neck - Guidelines and clinical case presentation (2-3 ca...
A. Tfayli - Head and neck - Guidelines and clinical case presentation (2-3 ca...A. Tfayli - Head and neck - Guidelines and clinical case presentation (2-3 ca...
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
  • 3.
  • 4.
  • 5.
  • 6.
  • 7.
  • 8.
  • 9.
  • 10.
  • 11.
  • 12.
  • 13.
  • 14.
  • 15.
  • 16.
  • 17. Challenges in Interpreting Phase II and III Clinical Trials Treatment Intensity
  • 18.
  • 19.
  • 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
  • 27. Cure esc BEACOPP Potential Strategies to Cure Advanced Stage Hodgkin Lymphoma ABVD High dose chemotherapy + autologous stem cell transplant Progression Endpoints = PFS RFS EFS TTP Endpoints = OS FF2F Progression Cure
  • 28. Potential Strategies to Cure Advanced Stage Hodgkin Lymphoma Study Regimen 5-y PFS (%) P 5-y OS (%) P Reference GHSG HD9 eBEACOPP 87 0.001 91 0.02 Diehl, 2003 COPP/ABVD 69 83 GISL HD2000 eBEACOPP 81 0.038 92 NS Federico, 2009 ABVD 68 84 GSM-HD eBEACOPP 85 0.004 89 0.39 Gianni, 2008 ABVD 73 86
  • 29. Kaplan-Meier analysis of the probability of the progression-free survival and overall survival according to intention to treat. Federico M et al. JCO 2009;27:805-811 ©2009 by American Society of Clinical Oncology Endpoint = PFS Endpoint = OS
  • 30.
  • 31.
  • 32.
  • 33.
  • 34. Challenges in Interpreting Phase II and III Clinical Trials Stage Migration & Lead Time Bias
  • 35. Lead time bias Challenges in Interpreting Phase II and III Clinical Trials Stage Migration & Lead Time Bias
  • 36. Correction for lead time bias Challenges in Interpreting Phase II and III Clinical Trials Stage Migration & Lead Time Bias
  • 37. Impact of new tests on the 131 Era 2 (1977) patients Challenges in Interpreting Phase II and III Clinical Trials Stage Migration & Lead Time Bias
  • 38. Challenges in Interpreting Phase II and III Clinical Trials Stage Migration & Lead Time Bias
  • 39. Challenges in Interpreting Phase II and III Clinical Trials Stage Migration & Lead Time Bias x
  • 40. Correction for lead time bias Challenges in Interpreting Phase II and III Clinical Trials Stage Migration & Lead Time Bias
  • 41.
  • 42.
  • 43.
  • 44.  
  • 45.
  • 46.
  • 47.
  • 48.
  • 49.
  • 52.  
  • 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)
  • 54.
  • 55. Response Results N=102 IRF Investigator Overall response rate (95% CI) 75% (65, 83) 72% (62, 80) Complete remission 34% 33% Partial remission 40% 38% Stable disease 22% 27% Progressive disease 3% 0% Not evaluable 1% 1%

Hinweis der Redaktion

  1. 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.