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Michael F Driscoll, MD Chief Fellow Medical Oncology / Hematology JGBCC University of Louisville

Update of 2010 American Society of Clinical Oncology (ASCO) Annual Meeting: Gastrointestinal Malignancies. Michael F Driscoll, MD Chief Fellow Medical Oncology / Hematology JGBCC University of Louisville. An Update on Gastrointestinal Cancer: Overview.

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Michael F Driscoll, MD Chief Fellow Medical Oncology / Hematology JGBCC University of Louisville

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  1. Update of 2010 American Society of Clinical Oncology (ASCO) Annual Meeting: Gastrointestinal Malignancies Michael F Driscoll, MD Chief Fellow Medical Oncology / Hematology JGBCC University of Louisville

  2. An Update on Gastrointestinal Cancer: Overview CRYSTAL/OPUS pooled analysis investigating the efficacy of cetuximab in KRAS wild-type tumors in patients with mCRC COIN: identification of patients with strongest responses to cetuximab + CT N0147: adjuvant mFOLFOX ± cetuximab in resected stage III colon cancer MACRO: maintenance Bev vs continued Bev + XELOX in mCRC PRIME: first-line panitumumab + FOLFOX4 vs FOLFOX4 in mCRC NASBP Protocol C10: evaluation of patients with stage IV CRC and asymptomatic primary tumors receiving mFOLFOX6 plus Bev without resection PRODIGE 4/ACCORD 11: FOLFIRINOX vs gemcitabine as first-line treatment for metastatic pancreatic cancer Phase II randomized comparison of modified DCF vs DCF in metastatic gastric cancer

  3. Colorectal Cancer

  4. CRYSTAL Trial FOLFIRI ± Cetuximab: Study Schema FOLFIRI5-FU bolus 400 mg/m2, 46-hr infusion 2400 mg/m2 + Irinotecan 180 mg/m2 +Leucovorin 400 mg/m2every 2 wks Patients with previously untreated EGFR-expressing metastatic colorectal cancer (N = 1217) FOLFIRI + Cetuximab5-FU bolus 400 mg/m2, 46-hr infusion 2400 mg/m2 + Irinotecan 180 mg/m2 +Leucovorin 400 mg/m2 every 2 wks +Cetuximab 400 mg/m2 initial dose, then 250 mg/m2 wkly • Patients stratified by region and ECOG performance score • Safety population: n = 1202 • ITT population: n = 1998 Van Cutsem E, et al. ASCO 2008. Abstract 2.

  5. CRYSTAL: PFS in Patients With the KRAS Mutation KRAS mutation (n = 192) HR: 1.07; P = .47 Cetuximab + FOLFIRI 1.0 FOLFIRI 0.9 Median PFS cetuximab + FOLIFIRI: 7.6 mos 0.8 Median PFS FOLIFIRI: 8.1 mos 0.7 0.6 PFS Estimate 0.5 0.4 0.3 0.2 0.1 0 0 2 4 6 8 10 12 14 16 Mos Van Cutsem E, et al. ASCO 2008. Abstract 2.

  6. CRYSTAL: PFS in Patients With WT KRAS WT KRAS (n = 348): HR: 0.68; P = .017 Cetuximab + FOLFIRI 1.0 FOLFIRI 0.9 Median PFS cetuximab + FOLIFIRI: 9.9 mos 0.8 Median PFS FOLIFIRI: 8.7 mos 0.7 1-yr PFS rate: 43% 0.6 PFS Estimate 0.5 0.4 0.3 1-yr PFS rate: 25% 0.2 0.1 0 0 2 4 6 8 10 12 14 16 18 Mos Van Cutsem E, et al. ASCO 2008. Abstract 2.

  7. KRAS Status and Efficacy of First-Line FOLFOX ± Cetuximab: OPUS Genomic DNA was isolated from archived tumor material KRAS mutation status of codons 12/13 was determined using a sensitive, quantitative PCR-based assay Population with tissue available for KRAS analysis (n = 233) was representative of overall ITT population (n = 337) in terms of demographics and efficacy parameters KRAS mutations detected in 42% (99/233) of evaluable samples Bokemeyer C, et al. ASCO 2008. Abstract 4000.

  8. OPUS: Results PFS and Response Rates by KRAS Mutation Status • The benefit from addition of cetuximab to standard treatment is higher forthe population with WT KRAS • No benefit could be shown of adding cetuximab to FOLFOX for patients with KRAS mutations Bokemeyer C, et al. ASCO 2008. Abstract 4000.

  9. An Update on Gastrointestinal Cancer: Overview CRYSTAL/OPUS pooled analysis investigating the efficacy of cetuximab in KRAS wild-type tumors in patients with mCRC COIN: identification of patients with strongest responses to cetuximab + CT N0147: adjuvant mFOLFOX ± cetuximab in resected stage III colon cancer MACRO: maintenance Bev vs continued Bev + XELOX in mCRC PRIME: first-line panitumumab + FOLFOX4 vs FOLFOX4 in mCRC NASBP Protocol C10: evaluation of patients with stage IV CRC and asymptomatic primary tumors receiving mFOLFOX6 plus Bev without resection PRODIGE 4/ACCORD 11: FOLFIRINOX vs gemcitabine as first-line treatment for metastatic pancreatic cancer Phase II randomized comparison of modified DCF vs DCF in metastatic gastric cancer

  10. CRYSTAL and OPUS: Objectives of Pooled Analysis • Investigate the efficacy of cetuximab in KRAS wild-type tumors and according to BRAF status in patients with mCRC • 1063 (89%) evaluable samples from CRYSTAL • 315 (93%) evaluable samples from OPUS • Primary endpoints • CRYSTAL: PFS (by independent review) • OPUS: OR (by independent review) • Secondary endpoint OS in both trials Bokemeyer C, et al. ASCO 2010. Abstract 3506.

  11. CRYSTAL/OPUS Pooled Analysis:Study Design Cetuximab + Chemotherapy Treat until disease progression, symptomatic deterioration, or unacceptable toxicity Patients with EGFR-positive mCRC Chemotherapy OPUS FOLFOX4 (cycles given q2w) Oxaliplatin 85 mg/m2 on Day 1 5-FU 400 mg/m2 bolus, then 600 mg/m2 on Days 1, 2 Leucovorin 200 mg/m2 on Day 1 Cetuximab 400 mg/m2 initial dose, then 250 mg/m2/wk CRYSTAL FOLFIRI (cycles given q2w) Irinotecan 180 mg/m2 on Day 1 5-FU: 400 mg/m2 bolus, then 600 mg/m2 on Days 1, 2 Leucovorin 200 mg/m2 on Day 1 Cetuximab 400 mg/m2 initial dose, then 250 mg/m2/wk

  12. Pooled Analysis of OS by Treatment Group for Patients with KRAS WT Tumors 1.0 0.9 FOLFIRI/FOLFOX4 + cetuximab (n = 398) median 23.5 mosFOLFIRI/FOLFOX4: (n = 447) median 19.5 mos 0.8 0.7 0.6 HR: 0.81 (95% CI: 0.69-0.94; P = .0062) Probability of OS 0.5 0.4 0.3 0.2 0.1 0 0 18 36 54 12 6 24 42 60 30 48 Mos Patients, nCT + cetuximabCT 398447 356395 296313 246227 177159 128112 8367 6548 2118 42 00 Bokemeyer C, et al. ASCO 2010. Abstract 3506. Reprinted with permission.

  13. Pooled Analysis of PFS by Treatment group for Patients with KRAS WT Tumors 1.0 0.9 FOLFIRI/FOLFOX4 + cetuximab (n = 398) median 9.6 mosFOLFIRI/FOLFOX4: (n = 447) median 7.6 mos 0.8 0.7 0.6 HR: 0.66 (95% CI: 0.55-0.80; P < .0001) Probability of PFS 0.5 0.4 0.3 0.2 0.1 0 0 12 4 8 20 16 Mos Patients, nCT + cetuximabCT 398447 286298 154128 4624 94 10 Bokemeyer C, et al. ASCO 2010. Abstract 3506. Reprinted with permission.

  14. CRYSTAL/OPUS Pooled Analysis:BRAF Mutation Associated With Poor Prognosis *Odds ratio. Bokemeyer C, et al. ASCO 2010. Abstract 3506. Reprinted with permission.

  15. CRYSTAL/OPUS Pooled Analysis:Conclusions • Statistically significant improvements in OS, PFS, and response rate associated with adding cetuximab to standard chemotherapy for first-line treatment of patients with mCRC and wild-type KRAS • In patients with wild-type KRAS and BRAF mutation, addition of cetuximab to chemotherapy resulted in numeric improvement in OS, PFS, and response rate • Investigators concluded that based on results of this pooled analysis, BRAF mutation status cannot be used as relevant predictive marker for addition of cetuximab to chemotherapy in first-line treatment of mCRC • However, BRAF mutation prognostic of poor survival outcome Bokemeyer C, et al. ASCO 2010. Abstract 3506.

  16. An Update on Gastrointestinal Cancer: Overview CRYSTAL/OPUS pooled analysis investigating the efficacy of cetuximab in KRAS wild-type tumors in patients with mCRC COIN: identification of patients with strongest responses to cetuximab + CT N0147: adjuvant mFOLFOX ± cetuximab in resected stage III colon cancer MACRO: maintenance Bev vs continued Bev + XELOX in mCRC PRIME: first-line panitumumab + FOLFOX4 vs FOLFOX4 in mCRC NASBP Protocol C10: evaluation of patients with stage IV CRC and asymptomatic primary tumors receiving mFOLFOX6 plus Bev without resection PRODIGE 4/ACCORD 11: FOLFIRINOX vs gemcitabine as first-line treatment for metastatic pancreatic cancer Phase II randomized comparison of modified DCF vs DCF in metastatic gastric cancer

  17. COIN: Patient Subsets With Best Responses to Addition of Cetuximab to CT Continuous Chemotherapy Administered until progression, toxicity, or patient choice 5-FU or Capecitabine + Oxaliplatin (n = 815) Patients with previously untreated advanced CRC Irinotecan-based second-line chemotherapy Cetuximab + Continuous Chemotherapy Administered until progression, toxicity, or patient choice Cetuximab + 5-FU or Capecitabine + Oxaliplatin (n = 815) Regimens OxFU administered q2w I-folinic acid 175 mg Oxaliplatin 85 mg/m2 5-FU 400 mg/m2 bolus, then 2400 mg/m2 over 46 hrs OxCap administered q3w Oxaliplatin 130 mg/m2 Capecitabine 1000 mg/m2 BID for 2 wks Maughan TS, et al. ASCO 2010. Abstract 3502.

  18. COIN: No Significant Difference in OS, PFS Between Treatment Arms, Pt Subsets Maughan TS, et al. ASCO 2010. Abstract 3502.

  19. COIN: Prognostic Effect of Mutational Status • Strong OS prognostic effect of KRAS, NRAS, and BRAF mutation status evident regardless of cetuximab use • Patients with wild-type KRAS have better prognosis vs mutated KRAS • Patients with mutated BRAF have the poorest prognosis Chemotherapy Chemotherapy + Cetuximab 12 Median PFS (Mos) 6 0 18 12 Median OS (Mos) 6 0 367 362 268 297 57 45 n = 289 292 340 815 366 815 Mutation Status BRAF mutation All patients KRAS wild type Any mutation Maughan TS, et al. ASCO 2010. Abstract 3502. Reprinted with permission. All wild type KRAS mutation

  20. COIN: Conclusions • No improvement in OS or PFS with addition of cetuximab to oxaliplatin-based chemotherapy for first-line treatment of advanced CRC • Response rate improved among patients with wild-type KRAS tumors • KRAS, BRAF, and NRAS mutation status strongly prognostic regardless of cetuximab treatment • Patients with mutated BRAF had poorest prognosis • Patients with wild-type KRAS, BRAF, and NRAS had the best prognosis Maughan TS, et al. ASCO 2010. Abstract 3502.

  21. An Update on Gastrointestinal Cancer: Overview CRYSTAL/OPUS pooled analysis investigating the efficacy of cetuximab in KRAS wild-type tumors in patients with mCRC COIN: identification of patients with strongest responses to cetuximab + CT N0147: adjuvant mFOLFOX ± cetuximab in resected stage III colon cancer MACRO: maintenance Bev vs continued Bev + XELOX in mCRC PRIME: first-line panitumumab + FOLFOX4 vs FOLFOX4 in mCRC NASBP Protocol C10: evaluation of patients with stage IV CRC and asymptomatic primary tumors receiving mFOLFOX6 plus Bev without resection PRODIGE 4/ACCORD 11: FOLFIRINOX vs gemcitabine as first-line treatment for metastatic pancreatic cancer Phase II randomized comparison of modified DCF vs DCF in metastatic gastric cancer

  22. N0147: Adjuvant mFOLFOX ± Cetuximab in Resected Stage III Colon Cancer 12 cycles mFOLFOX6 Oxaliplatin 85 mg/m2 + Leucovorin 400 mg/m2 + 5-FU 2400 mg/m2 (infused over 46 hrs) q2w (n = 1283) Patients with stage III colon cancer (N = 2581) mFOLFOX6 + Cetuximab 400 mg/m2 loading dose then 250 mg/m2 on Days 1, 8 (n = 1298) Goldberg RM, et al. ASCO 2010. Abstract 3508.

  23. N0147:Duration of Therapy Shorter With Cetuximab Addition vs mFOLFOX6 Alone Wild-Type KRAS Mutant KRAS Goldberg RM, et al. ASCO 2010. Abstract 3508. Reprinted with permission.

  24. Trend Toward Improved DFS, OS With mFOLFOX6 vs mFOLFOX6 + Cetuximab Goldberg RM, et al. ASCO 2010. Abstract 3508.

  25. Pts With Mutant KRAS More Likely to Have Disease Progression or Death Goldberg RM, et al. ASCO 2010. Abstract 3508.

  26. N0147:Targeting EGFR in Stage III Colorectal Cancer • Cetuximab does not improve adjuvant chemotherapy for rates of DFS and OS in resected stage III colon cancer • Increased toxicity • KRAS mutation associated with poor prognosis vs wild-type KRAS • EGFR-targeted antibodies likely not feasible as part of adjuvant regimens for stage III colon cancer Goldberg RM, et al. ASCO 2010. Abstract 3508.

  27. Prognostic and/or Predictive Value of KRAS in CRC 1. Bokemeyer C, et al. J Clin Oncol. 2009;27:663-671. 2. Van Cutsem E, et al. N Engl J Med. 2009;360:1408-1417. 3. Amado RG, et al. J Clin Oncol. 2008;26:1626-1634.4. Douillard J, et al. ASCO 2010. Abstract 3528. 5. Andreyev HJ, et al. J Natl Cancer Inst. 1998;90:675-684. 6. Andreyev HJ, et al. Br J Cancer. 2001;85:692-696. 7. Richman SD, et al. J Clin Oncol. 2009;27:5931-5937. 8. Maughan TS, et al. ASCO 2010. Abstract 3502. 9. Goldberg RM, et al. ASCO 2010. Abstract 3508. 10. Karapetis CS, et al. N Engl J Med. 2008;359:1757-1765. 11. Tol J, et al. N Engl J Med. 2009;360:563-572. 12. Hecht JR, et al. J Clin Oncol. 2009;27:672-680. • Predictive of treatment response • Anti-EGFR antibodies not beneficial in patients with KRAS mutations[1-4] • Prognostic of outcome • Yes: RASCAL,[5,6] FOCUS,[7] COIN,[8] N0147[9] • No: cetuximab and panitumumab monotherapy trials,[3,10] CAIRO-2,[11] PACCE[12] • Maybe: CRYSTAL[2]

  28. An Update on Gastrointestinal Cancer: Overview CRYSTAL/OPUS pooled analysis investigating the efficacy of cetuximab in KRAS wild-type tumors in patients with mCRC COIN: identification of patients with strongest responses to cetuximab + CT N0147: adjuvant mFOLFOX ± cetuximab in resected stage III colon cancer MACRO: maintenance Bev vs continued Bev + XELOX in mCRC PRIME: first-line panitumumab + FOLFOX4 vs FOLFOX4 in mCRC NASBP Protocol C10: evaluation of patients with stage IV CRC and asymptomatic primary tumors receiving mFOLFOX6 plus Bev without resection PRODIGE 4/ACCORD 11: FOLFIRINOX vs gemcitabine as first-line treatment for metastatic pancreatic cancer Phase II randomized comparison of modified DCF vs DCF in metastatic gastric cancer

  29. MACRO: Maintenance Bev vs Continued Bev + XELOX in Patients With mCRC XELOX + Bevacizumab (n = 239) Induction Therapy XELOX + Bevacizumab 6 cycles Disease progression, severe toxicity, or consent withdrawal Patients with previously untreated mCRC (N = 480) Bevacizumab (n = 241) Maintenance cycles administered q3w: Oxaliplatin 130 mg/m2 IV on Day 1 Capecitabine 1000 mg/m2 BID PO on Days 1-14 Bevacizumab 7.5 mg/kg IV on Day 1 Tabernero J, et al. ASCO 2010. Abstract 3501.

  30. MACRO: Duration of PFS Comparable Between Bev vs XELOX + Bev *Median follow-up: 20.4-21.1 mos. • No significant difference between treatment arms in any efficacy outcome • Noninferiority of bevacizumab vs XELOX + bevacizumab cannot be confirmed • The median PFS HR 95% CI (0.89-1.37) beyond the planned noninferiority limit of 1.32 Tabernero J, et al. ASCO 2010. Abstract 3501.

  31. MACRO: Conclusions • After bevacizumab + XELOX induction therapy for patients with mCRC, maintenance bevacizumab comparable to continued bevacizumab + XELOX • No significant difference in any efficacy outcome between arms • Single-agent bevacizumab may be a feasible option for patients receiving bevacizumab + XELOX as induction therapy Tabernero J, et al. ASCO 2010. Abstract 3501.

  32. An Update on Gastrointestinal Cancer: Overview CRYSTAL/OPUS pooled analysis investigating the efficacy of cetuximab in KRAS wild-type tumors in patients with mCRC COIN: identification of patients with strongest responses to cetuximab + CT N0147: adjuvant mFOLFOX ± cetuximab in resected stage III colon cancer MACRO: maintenance Bev vs continued Bev + XELOX in mCRC PRIME: first-line panitumumab + FOLFOX4 vs FOLFOX4 in mCRC NASBP Protocol C10: evaluation of patients with stage IV CRC and asymptomatic primary tumors receiving mFOLFOX6 plus Bev without resection PRODIGE 4/ACCORD 11: FOLFIRINOX vs gemcitabine as first-line treatment for metastatic pancreatic cancer Phase II randomized comparison of modified DCF vs DCF in metastatic gastric cancer

  33. PRIME: First-line Panitumumab + FOLFOX4 vs FOLFOX4 in mCRC Stratified by ECOG PS (0-1 vs 2) and geographic region Panitumumab 6.0 mg/kg every 2 wks + FOLFOX4 (n = 593) Patients with previously untreated mCRC (N = 1183) FOLFOX4 (n = 590) FOLFOX4 (cycles given q2w) Oxaliplatin 85 mg/m2 on Day 1 5-FU 400 mg/m2 bolus, then 600 mg/m2 on Days 1, 2 Leucovorin 200 mg/m2 on Day 1 Douillard J, et al. ASCO 2010. Abstract 3528.

  34. PRIME: PFS, OS by KRAS Status Douillard J, et al. ASCO 2010. Abstract 3528.

  35. PRIME Exploratory Analysis: Efficacy of Panitumumab + FOLFOX4 by Skin Toxicity *Landmark analysis of patients with PFS duration ≥ 28 days. Douillard J, et al. ASCO 2010. Abstract 3528.

  36. PRIME: Conclusions • In patients with previously untreated mCRC receiving panitumumab + FOLFOX4, grade 2-4 skin toxicity associated with significantly longer PFS and OS vs grade 0/1 skin toxicity, regardless of KRAS mutationstatus • Panitumumab + FOLFOX4 associated with significantly improved PFS in patients with KRAS wild-type tumors, significantly worse PFS in patients with KRAS-mutated tumors • Similar trends in OS; no differences in objective response rate between groups Douillard J, et al. ASCO 2010. Abstract 3528.

  37. An Update on Gastrointestinal Cancer: Overview CRYSTAL/OPUS pooled analysis investigating the efficacy of cetuximab in KRAS wild-type tumors in patients with mCRC COIN: identification of patients with strongest responses to cetuximab + CT N0147: adjuvant mFOLFOX ± cetuximab in resected stage III colon cancer MACRO: maintenance Bev vs continued Bev + XELOX in mCRC PRIME: first-line panitumumab + FOLFOX4 vs FOLFOX4 in mCRC NASBP Protocol C10: evaluation of patients with stage IV CRC and asymptomatic primary tumors receiving mFOLFOX6 plus Bev without resection PRODIGE 4/ACCORD 11: FOLFIRINOX vs gemcitabine as first-line treatment for metastatic pancreatic cancer Phase II randomized comparison of modified DCF vs DCF in metastatic gastric cancer

  38. NASBP Protocol C10 • 74% of patients with stage IV CRC not eligible for curable resection • Asymptomatic primary tumor present in 75% of those patients • Study evaluated intact primary tumor-related morbidity in patients with stage IV CRC with asymptomatic primary tumor receiving mFOLFOX6 plus bevacizumab who have not undergone resection • Primary endpoint • Primary tumor events requiring surgery • Bleeding • Perforation or fistula formation • Obstruction • Primary tumor events leading to death McCahill LE, et al. ASCO 2010. Abstract 3527.

  39. NASBP Protocol C10: Low Rate of Tumor Events Requiring Surgery • 10 patients (11.6%) required surgery • Obstruction: n = 8 • Perforation: n = 1 • Pain: n = 1 • 2 patients (2.3%) died • Perforation: n = 1 • Obstruction: n = 1 • At Month 24, estimated cumulative incidence of major morbidity associated with intact primary tumor: 16.3% (95% CI: 7.6% to 25.1%) McCahill LE, et al. ASCO 2010. Abstract 3527.

  40. NASBP Protocol C10: Conclusions In patients with unresectable stage IV colorectal cancer with an asymptomatic primary tumor, treatment with mFOLFOX6 plus bevacizumab associated with a low rate of primary tumor events requiring surgery or leading to death Median OS: 19.9 mos Low rate of primary events (13.9%) suggests these patients can be spared initial noncurative resection of primary tumor McCahill LE, et al. ASCO 2010. Abstract 3527.

  41. Pancreatic Cancer

  42. An Update on Gastrointestinal Cancer: Overview CRYSTAL/OPUS pooled analysis investigating the efficacy of cetuximab in KRAS wild-type tumors in patients with mCRC COIN: identification of patients with strongest responses to cetuximab + CT N0147: adjuvant mFOLFOX ± cetuximab in resected stage III colon cancer MACRO: maintenance Bev vs continued Bev + XELOX in mCRC PRIME: first-line panitumumab + FOLFOX4 vs FOLFOX4 in mCRC NASBP Protocol C10: evaluation of patients with stage IV CRC and asymptomatic primary tumors receiving mFOLFOX6 plus Bev without resection PRODIGE 4/ACCORD 11: FOLFIRINOX vs gemcitabine as first-line treatment for metastatic pancreatic cancer Phase II randomized comparison of modified DCF vs DCF in metastatic gastric cancer

  43. PRODIGE 4/ACCORD 11 Trial Design RANDOMIZE for both arms: FOLFIRINOX (n = 171) CT scans: obtained every 2 mons Patients with metastaticpancreaticcancer (N = 342) 6 mos of chemotherapy recommended Gemcitabine (n = 171) Stratified by • Center • Performance score 0 vs 1 • Location of the tumor: head vs other location of the primary Conroy T, et al. ASCO 2010. Abstract 4010. Reprinted with permission.

  44. PRODIGE 4/ACCORD 11: Progression-Free Survival Median PFS, Mos 6.4 3.3 1.00 FOLFIRINOX Gemcitabine 0.75 HR: 0.47 (95% CI: 0.37-0.59; P < .0001) Probability 0.50 0.25 0 0 3 6 9 12 15 18 21 24 27 30 33 36 Mos Patients at Risk, nGemcitabineFOLFIRINOX 171171 88121 2685 842 517 27 04 01 01 Conroy T, et al. ASCO 2010. Abstract 4010.

  45. PRODIGE 4/ACCORD 11: Overall Survival Median OS, Mos 11.1 6.8 1.00 FOLFIRINOX Gemcitabine 0.75 HR: 0.57 (95% CI: 0.45-0.73) Stratified log rank test P < .0001 Probability 0.50 0.25 0 0 3 6 9 12 15 18 21 24 27 30 33 36 Mos Patients at Risk, nGemcitabineFOLFIRINOX 171171 134146 89116 4881 2862 1434 720 613 39 35 23 22 22 Conroy T, et al. ASCO 2010. Abstract 4010.

  46. PRODIGE 4/ACCORD 11: Safety Conroy T, et al. ASCO 2010. Abstract 4010.

  47. PRODIGE 4/ACCORD 11: Conclusions • In patients with metastatic pancreatic cancer FOLFIRINOX associated with significant improvements in PFS and OS vs gemcitabine • Median OS: 11.1 mos; reduced risk of disease progression by 53% • FOLFIRINOX associated with significantly increased incidence of adverse events, although significantly (P = .001) delays QoL degradation vs gemcitabine • Investigators asserted that FOLFIRINOX potential new standard of care in this setting Conroy T, et al. ASCO 2010. Abstract 4010.

  48. An Update on Gastrointestinal Cancer: Overview CRYSTAL/OPUS pooled analysis investigating the efficacy of cetuximab in KRAS wild-type tumors in patients with mCRC COIN: identification of patients with strongest responses to cetuximab + CT N0147: adjuvant mFOLFOX ± cetuximab in resected stage III colon cancer MACRO: maintenance Bev vs continued Bev + XELOX in mCRC PRIME: first-line panitumumab + FOLFOX4 vs FOLFOX4 in mCRC NASBP Protocol C10: evaluation of patients with stage IV CRC and asymptomatic primary tumors receiving mFOLFOX6 plus Bev without resection PRODIGE 4/ACCORD 11: FOLFIRINOX vs gemcitabine as first-line treatment for metastatic pancreatic cancer Phase II randomized comparison of modified DCF vs DCF in metastatic gastric cancer

  49. Phase II Randomized Comparison of Modified DCF vs DCF To develop a DCF-like regimen that is more tolerable than parent DCF, to which a targeted agent could be safely added Modified DCF (n = 56) Patients with previously untreated metastatic gastric/GEJ adenocarcinoma (N = 87) R DCF + G-CSF (n = 31) Stratified by • GEJ/gastric • Measurable/nonmeasurable Shah MA, et al. ASCO 2010. Abstract 4014.

  50. Modified DCF vs DCF: Treatment Arms Shah MA, et al. ASCO 2010. Abstract 4014.

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