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This house believes that FOLFIRINOX is the best treatment for patients with metastatic pancreatic adenocarcinoma - PowerPoint PPT Presentation


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This house believes that FOLFIRINOX is the best treatment for patients with metastatic pancreatic adenocarcinoma. Pro Marc YCHOU Montpellier. R A N D O M I Z E. Oxaliplatin 85 mg/m 2 over 2 h Leucovorin 400 mg/ m 2 over 2 h

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Presentation Transcript
slide1

This house believesthat FOLFIRINOX is the best treatment for patients withmetastaticpancreaticadenocarcinoma

Pro

Marc YCHOU

Montpellier

prodige 4 accord 11 trial design

R

A

N

D

O

M

I

Z

E

Oxaliplatin 85 mg/m2 over 2 h

Leucovorin 400 mg/m2over 2 h

Irinotecan 180 mg/m2in 90 mn infusion5-FU 400 mg/m2bolus

5-FU 2400 mg/m2on 46-h infusion

Folfirinox

Gemcitabine

Prodige 4 - ACCORD 11 trial design

1000 mg/m2 over 30 minutes

weekly x 7/8 and then weekly x 3/4

overall survival
Overall Survival

Gemcitabine

Folfirinox

accord 11 questions about this trial
ACCORD 11: QUESTIONS ABOUT THIS TRIAL
  • Didwe have a coherentrationale to test FOLFIRINOX in a phase III trial ?
  • Gemcitabine : a relevant control arm ?
  • FOLFIRINOX: efficacious but tootoxic ?
  • Study population: tooselected ?
  • DidFOLFIRINOXregimendegradeQuality of Life ?
a phase i trial to assess the triple combination
A Phase I trial to assess the triple combination
  • Fixed dose level of simplified LV5FU2
  • 8 dose levelsplanned for CPT-11 and L-OHP at day 1

Ychou M et al. AnnalsOncol 2003;14(3):481-9

the recommended phase ii dose

Bolus 5-FU 400 mg/m2

2 h

Oxaliplatin

85 mg/m2

Leucovorin

400 mg/m2

Continuous 5-FU

2.400 mg/m2

Irinotecan

180 mg/m2

2 h

46 h

1 h 30

The recommendedPhase II Dose

Simplified LV5FU+ 85 mg/m2 l-OHP + 180 mg/m2 CPT-11

background
Background
  • Folfirinox regimenassessed in a phase II study(n=35)
    • Promisingregimen in M1 patients with good PS
    • Mediansurvival of 9.5 months

Conroy T et al. J Clin Oncol 2005;23:1228-36

  • A randomizedphase II-III studycomparing Folfirinox regimen to gemcitabinealonewaslaunched
  • Results of the phase II portion (n=88) presentedat the ASCO 2007 (objective: RR ≥ 24% in the Folfirinox arm)
    • 31.8% RR in the Folfirinox arm vs 11.4% in the gemcitabinearm

Ychou M et al. J Clin Oncol 2007;25:18S:201s

Due to encouraginginterimresults, the trial continued as a phase III study

accord 11 questions about this trial1
ACCORD 11: QUESTIONS ABOUT THIS TRIAL
  • Didwe have a coherentrationale to test FOLFIRINOX in a phase III trial ?
  • Gemcitabine : a relevant control arm ?
  • FOLFIRINOX: efficacious but tootoxic ?
  • Study population: tooselected ?
  • Did FOLFIRINOX regimendegradeQuality of Life ?
slide9

Burris et al. : Gemcitabine vs 5FU

  • 126 locallyadvanced or symptomaticpancreas ADK
  • Kanorfskybetween 50% and 80%
  • Primary endpoint: clinicalbenefit(pain. PS. body weight)

R

Single blind

5FU 600 mg/m². 30' weekly

(n = 63)

Gemcitabine 1000 mg/m² 30' weekly

(n = 63)

Burriset al. JCO Jun 1. 1997:2403-13

burris et al efficacy
Burris et al. : Efficacy
  • Gemcitabine is more effective than 5-FU in alleviation of somedisease-related symptoms
  • Gemcitabine confers a modest survival advantage

Burriset al. JCO Jun 1. 1997:2403-13

prognosis of patients with metastatic pancreatic cancer is poor
Prognosis of patients with metastatic pancreatic cancer is poor
  • 5-year survival rates is 6%
  • Although gemcitabine became the reference treatment almost 15 years ago, attempts to improve outcomes since then have been disappointing

*statistically significant (p<0.05)

1. Burris et al. J ClinOncol 1997; 2. Berlin et al. J ClinOncol 2002; 3. Louvet et al. J ClinOncol 2005; 4. Heinemann et al. J ClinOncol 2006; 5. Moore et al. J ClinOncol 2007; 6. Poplin et al. J ClinOncol 2009; 7. Cunningham et al. J ClinOncol 2008; 8. Cunningham et al. J ClinOncol 2009; 9. Kindler et al. ASCO 2007; 10. Van Cutsem et al. J ClinOncol 2009; 11. Philip et al. ASCO 2007.

gemcitabine alone in locally advanced and metastatic pancreatic cancer
Gemcitabine alone in locally advanced and metastatic pancreatic cancer
  • ACCORD 11 trial: results for gemcitabineare comparable to thoseobservedacross a variety of studies

* Onlymetastatic patients

accord 11 questions about this trial2
ACCORD 11: QUESTIONS ABOUT THIS TRIAL
  • Didwe have a coherentrationale to test FOLFIRINOX in a phase III trial ?
  • Gemcitabine : a relevant control arm ?
  • FOLFIRINOX: efficacious but tootoxic ?
  • Study population: tooselected ?
  • Did FOLFIRINOX regimendegradeQuality of Life ?
safety main adverse events in accord 11
Safety: main adverse events in ACCORD 11
  • One toxicdeathin each arm

*No prophylactic use of G-CSF

maximum grade 3 4 toxicity in the methep trial liver metastases from crc
Maximum Grade 3/4 toxicity in the METHEP trial (liver metastases from CRC)

* Prophylactic use of GCS-F except in 4 patients**

accord 11 questions about this trial3
ACCORD 11: QUESTIONS ABOUT THIS TRIAL
  • Didwe have a coherentrationale to test FOLFIRINOX in a phase III trial ?
  • Gemcitabine : a relevant control arm ?
  • FOLFIRINOX: efficacious but tootoxic ?
  • Study population: tooselected ?
  • Did FOLFIRINOX regimendegradeQuality of Life ?
accord 11 toxicity of folfirinox in patients with biliary stent
ACCORD 11: Toxicity of Folfirinox in patients withbiliarystent

 Similarrisk of developing infections and hematologictoxicity

accord 11 questions about this trial4
ACCORD 11: QUESTIONS ABOUT THIS TRIAL
  • Didwe have a coherentrationale to test FOLFIRINOX in a phase III trial ?
  • Gemcitabine : a relevant control arm ?
  • FOLFIRINOX: efficacious but tootoxic ?
  • Study population: tooselected?
  • Did FOLFIRINOX regimendegradeQuality of Life ?
slide23

Change in mean QLQ-C30 score over time

(A) Global health status

(B) Diarrhea

accord 11 questions about this trial5
ACCORD 11: QUESTIONS ABOUT THIS TRIAL
  • A coherentrationale to test FOLFIRINOX in a phase III trial ?
  • Gemcitabine : a relevant control arm ?
  • FOLFIRINOX: tootoxic?
  • Study population: tooselected?
  • Did FOLFIRINOX regimendegradeQualityof Life ?

Yes

Yes

No, toxicityismanageable

Generalizable to a quite large population

No

conclusion
Conclusion
  • I do believethat FOLFIRINOX is the best treatment for patients withmetastaticpancreaticadenocarcinoma if :
  • Bilirubin <1.5 UNL
  • PS 0-1
  • Age< 75
  • This combination is now tested in the adjuvant setting: ACCORD/PRODIGE 24 trial