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Norman Wolmark, MD Colorectal Cancer Update Think Tank Meeting June 24, 2005

A Phase III Trial Comparing FULV to FULV + Oxaliplatin in Stage II or III Carcinoma of the Colon: Results of NSABP-C-07. Norman Wolmark, MD Colorectal Cancer Update Think Tank Meeting June 24, 2005. MOSAIC. Stage ll+lll. â. Randomize. å. æ. LV5FU2. FOLFOX4. DFS. 1.0 0.9 0.8 0.7 0.6

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Norman Wolmark, MD Colorectal Cancer Update Think Tank Meeting June 24, 2005

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  1. A Phase III Trial Comparing FULV to FULV + Oxaliplatin in Stage II or III Carcinoma of the Colon: Results of NSABP-C-07 Norman Wolmark, MDColorectal Cancer Update Think Tank MeetingJune 24, 2005

  2. MOSAIC Stage ll+lll â Randomize å æ LV5FU2 FOLFOX4

  3. DFS 1.0 0.9 0.8 0.7 0.6 0.5 3-year FOLFOX (n = 1,123) 77.8% LV5FU2 (n = 1,123) 72.9% Proportion of patients Hazard ratio: 0.77 [0.65 – 0.92] p < 0.01 0 10 20 30 40 50 DFS (months) 23% risk reduction in the FOLFOX arm Source: de Gramont A. Presentation. ASCO 2003.

  4. On November 4, 2004, the FDA approved oxaliplatin in combination with infusional FULV for adjuvant Stage III colon cancer. The approval was based on improvement in DFS…

  5. NSABP-C-07 Stage ll+lll â Stratification: Number of positive nodes â Randomize å æ FULV Bolus 5-FU/leucovorin FLOX Bolus 5-FU/leucovorin + oxaliplatin

  6. NSABP-C-07: 5-FU/LV versus 5-FU/LV plus Oxaliplatin in Stage II/III Colon Cancer FU 500 Rest LV 500 R x 3 FU 500 LV 500 Rest OHP 85 2hr Week 1 2 3 4 5 6 7 8 Source: Wolmark N. Presentation. ASCO 2005.

  7. NSABP-C-07 • Opened: 02-00 • Closed: 11-02 • Accrual: 2,407 • MTS: 34 mo. • Endpoint: 3 yr DFS • Event: first recurrence, second primary, death (any cause) • 89% power to detect:5.4% ↑ DFS Source: Wolmark N. Presentation. ASCO 2005.

  8. C-07Accrual Source: Wolmark N. Presentation. ASCO 2005.

  9. C-07Patient Characteristics Source: Wolmark N. Presentation. ASCO 2005.

  10. C-07Overall Toxicity (%) Source: Wolmark N. Presentation. ASCO 2005.

  11. C-07 Sanofi-NCI Neurotoxicity • Gr I P/D that do not interfere with function • Gr II P/D interfering with function, but not ADL • Gr III P/D with pain or interference with ADL • Gr IV Persistent P/D that are disabling or life-threatening P = paresthesia; D = dysesthesia; ADL = activities of daily living Source: www.eloxatin.com/hep/patientmgmt5.asp

  12. C-07 Sanofi-NCI Neurotoxicity Grade ≥ 1 (All) Neurotoxicity (%) Grade > 1 (All) Neurotoxicity (%) 100 80 60 40 20 0 100 80 60 40 20 0 85.4 85.4 29.4 During Tx During Tx 12 months Source: Wolmark N. Presentation. ASCO 2005.

  13. C-07 Sanofi-NCI Neurotoxicity Grade III Neurotoxicity (%) 10 8 6 4 2 0 8 0.5 During Tx 12 months Source: Wolmark N. Presentation. ASCO 2005.

  14. OxaliplatinProtocol-Stipulated Cumulative Dose • C-07 765 mg/m2 • MOSAIC 1,020 mg/m2 Source: Wolmark N. Presentation. ASCO 2005.

  15. Percent of Full Dose Oxaliplatin/Cycle 100 80 60 40 20 0 86.9 68.6 62.5 1 2 3 73% received protocol-stipulated cumulative dose Source: Wolmark N. Presentation. ASCO 2005.

  16. C-07Bowel Wall Injury Source: SmithRE et al. Proc ASCO GI2004.

  17. C-07Deaths During Treatment Source: Wolmark N. Presentation. ASCO 2005.

  18. C-07 Disease-Free Survival 1.0 0.9 0.8 0.7 0.6 0.5 Events 3y DFS FLOX 272 76.5% FULV 332 71.6% Proportion of patients p < 0.004 HR: 0.79 [0.67 – 0.93] 0 1 2 3 4 Years 21% risk reduction Source: Wolmark N. Presentation. ASCO 2005.

  19. The global test for interaction between treatment and tumor stage (II+III) was not significant (p = 0.70).

  20. Benefit from Oxaliplatin in NSABP-C-07 and MOSAIC Trials Sources: Wolmark N. Presentation. ASCO 2005; de Gramont A. Presentation. ASCO 2003.

  21. Conclusions • The addition of oxaliplatin to weekly bolus FULV significantly improves 3-year DFS in patients with Stage II and III colon cancer. • The data confirm and extend the results of the MOSAIC trial. • The benefit of oxaliplatin does not appear to be dependent on the schedule of FULV administration. • The data support the use of weekly bolus FULV in combination with oxaliplatin in adjuvant colon cancer.

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