Copyright © 2011 Research To Practice. All rights reserved.
Case presented by Dr Schwartz
• 44 yo woman with 4 mo hx of abdominal pain
– Imaging = pancreatic mass in body/tail
• 9/1/10: Distal pancreatectomy = well-circumscribed 6 cm adeno CA with perineural invasion, no nodes, but 4mm liver lesion mets
• 9/27/10: CA19-9 >6,000 and PET/CT extensive liver involvement FOLFIRINOX as per ACCORD trial
– 3 cycles complete – disease responding and CA19-9 ↓85%
– Well tolerated except asymptomatic neutropenia
Copyright © 2011 Research To Practice. All rights reserved.
Randomized Phase III Trial Comparing FOLFIRINOX versus Gemcitabine as First-Line Treatment for Metastatic Pancreatic Adenocarcinoma: Preplanned Interim Analysis Results of the PRODIGE 4/ACCORD 11 TrialConroy T et al. Proc ASCO 2010;Abstract 4010.
Copyright © 2011 Research To Practice. All rights reserved.Conroy T et al. Proc ASCO 2010;Abstract 4010.
AE (% per patient)FOLFIRINOX
(n = 167)Gemcitabine
(n = 169) p-value
Febrile neutropenia 5.4 0.6 0.009
Thrombocytopenia 9.1 2.4 0.008
Peripheral neuropathy 9.0 0 0.0001
Vomiting 14.5 4.7 0.002
Diarrhea 12.7 1.2 0.0001
ALT 7.3 18.6 0.0022
FOLFIRINOX regimen is more toxic, but toxicity is manageable
PRODIGE 4/ACCORD 11:Selected Grade 3/4 Adverse Events (AE)
Copyright © 2011 Research To Practice. All rights reserved.Conroy T et al. Proc ASCO 2010;Abstract 4010.
Efficacy ParameterFOLFIRINOX
(n = 171)Gemcitabine
(n = 171)Hazard ratio
(p-value)
Disease control rate (CR + PR + SD)
70.2% (0.6% + 31% + 38.6%)
50.9% (0% + 9.4% + 41.5%)
— (0.0003)
Progression 15.2% 34.5% —
Progression-free survival
6.4 months 3.3 months 0.47 (<0.0001)
Overall survival 11.1 months 6.8 months 0.57 (<0.0001)
FOLFIRINOX recommended as new standard of care for metastatic pancreatic cancer with bilirubin <1.5 ULN and PS 0-1
PRODIGE 4/ACCORD 11: Efficacy
Median follow-up: 26.6 months
Copyright © 2011 Research To Practice. All rights reserved.
Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trialNeoptolemos JP et al. JAMA 2010; 304(10); 1073-81
Refinement of adjuvant therapy for pancreatic cancerO’Reilly EM et al.JAMA 2011; 304(10); 1124-5.
Copyright © 2011 Research To Practice. All rights reserved.
Case presented by Dr Schwartz
• 44 yo woman with 4 mo hx of abdominal pain
– Imaging = pancreatic mass in body/tail
• 9/1/10: Distal pancreatectomy = well-circumscribed 6 cm adeno CA with perineural invasion, no nodes, but 4mm liver lesion mets
• 9/27/10: CA19-9 >6,000 and PET/CT extensive liver involvement FOLFIRINOX as per ACCORD trial
– 3 cycles complete – disease responding and CA19-9 ↓85%
– Well tolerated except asymptomatic neutropenia
Copyright © 2011 Research To Practice. All rights reserved.
Trial Median Overall Survival
ESPAC-1‡
Chemoradiotherapy
No chemoradiotherapy
Chemotherapy
No chemotherapy
15.9 mos17.9 mos20.1 mos15.5 mos
ESPAC-3
5-FU/folinic acid
Gemcitabine
23.0 mos23.6 mos
Efficacy Results from the European Study Group for Pancreatic Cancer (ESPAC) 1 and 3 Trials
Neoptolemos JP et al. N Engl J Med 2004;350:1200-10; Neoptolemos JP et al. JAMA 2010;304(10):1073-81.
‡ Median follow-up: 47 monthsMedian follow-up: 34 months
Copyright © 2011 Research To Practice. All rights reserved.
Case presented by Dr Schwartz
• 44 yo woman with 4 mo hx of abdominal pain
– Imaging = pancreatic mass in body/tail
• 9/1/10: Distal pancreatectomy = well-circumscribed 6 cm adeno CA with perineural invasion, no nodes, but 4mm liver lesion mets
• 9/27/10: CA19-9 >6,000 and PET/CT extensive liver involvement FOLFIRINOX as per ACCORD trial
– 3 cycles complete – disease responding and CA19-9 ↓85%
– Well tolerated except asymptomatic neutropenia
Copyright © 2011 Research To Practice. All rights reserved.
Results of a Phase 1/2 Study of Nab-Paclitaxel Plus Gemcitabine in Patients with Advanced Pancreatic Cancer with SPARC and CA19-9 Correlatives
Ramanathan R et al. Proc ESMO 2010;Abstract 743P.
Copyright © 2011 Research To Practice. All rights reserved.Ramanathan R et al. Proc ESMO 2010;Abstract 743P.
Efficacy (n = 67)
Complete response 4%
Partial response 42%
Stable disease >16 weeks 18%
Median survival (all arms) 10.3 months
• All evaluable patients had >20% decrease in CA19-9 levels • Survival collated with SPARC signature (13.6 versus 8.1 months in
low vs high risk, p-value = 0.02)
Efficacy of Nab Paclitaxel + Gemcitabine for Advanced Pancreatic Cancer
Copyright © 2011 Research To Practice. All rights reserved.
No prior radiotherapy, surgery, chemotherapy or investigational drug therapyNo brain metastasesECOG PS 0-1
Phase II Trial Schema: Hedgehog Inhibitors (GDC-0449) for Metastatic Adenocarcinoma of the Pancreas
Gemcitabine 1000 mg/m2 + nab paclitaxel 125 mg/m2 d1, 8, 15 q4wk (cycle 1)
Gemcitabine 1000 mg/m2 + nab paclitaxel 125 mg/m2 d1, 8, 15 q4wk + GDC-0449 150 mg qd (subsequent cycles)
Accrual: N = 80 (open)
Primary Endpoint: 2-year progression-free survivalSecondary Endpoints: 2-year overall survival, tumor response, hedgehog signaling pathway downregulation, pancreatic cancer stem cells in tissue and peripheral blood
www.ClinicalTrials.gov, March 2011.
Copyright © 2011 Research To Practice. All rights reserved.
Gemcitabine plus erlotinib (GE) followed by capecitabine (C) versus capecitabine plus erlotinib (CE) followed by gemcitabine (G) in advanced pancreatic cancer (APC): A randomized, cross-over phase III trial of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Boeck et al. Proc ASCO 2010;Abstract LBA4011.
Copyright © 2011 Research To Practice. All rights reserved.
No prior chemotherapy or radiotherapyNo CNS metastasesNo external biliary drain
GAMMA: Phase III Trial on Gemcitabine and AMG 479 in Advanced Pancreatic Adenocarcinoma
AMG 479 12 mg/kg d1 and 15 q4wk + Gemcitabine 1000 mg/m2 d1, 8, 15 q4wk
RPlacebo d1 and 15 q4wk + Gemcitabine 1000 mg/m2 d1, 8, 15 q4wk
Accrual: N = 825 (open)
AMG 479 20 mg/kg d1 and 15 q4wk + Gemcitabine 1000 mg/m2 d1, 8, 15 q4wk
Primary Endpoint: 2-year overall survivalSecondary Endpoints: 2-year progression-free survival, objective response rate, time to disease progression, disease control rate and adverse events
www.ClinicalTrials.gov, March 2011.
Copyright © 2011 Research To Practice. All rights reserved.
Faculty
National GI Tumor Board
Clinical Investigators Provide Their Perspectives on Current Cases of Gastrointestinal Cancer
Friday, January 21, 20117:00 PM – 9:30 PM
San Francisco, California
ModeratorNeil Love, MD
Eileen M O’Reilly, MDEric Van Cutsem, MD, PhD Andrew X Zhu, MD, PhD
Charles D Blanke, MDDavid Cunningham, MDSteven A Curley, MD