case presented by dr schwartz

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


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


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.


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


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


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.


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.


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.


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

case presented by dr schwartz

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