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.

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Presentation transcript:

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

  Randomize LV5FU2 Stage ll+lll FOLFOX4 MOSAIC

% risk reduction in the FOLFOX arm DFS (months) Hazard ratio: 0.77 [0.65 – 0.92] p < year FOLFOX (n = 1,123) 77.8% LV5FU2 (n = 1,123) 72.9% Proportion of patients Source: de Gramont A. Presentation. ASCO DFS

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…

  Randomize FULV Bolus 5-FU/leucovorin Stratification: Number of positive nodes FLOX Bolus 5-FU/leucovorin + oxaliplatin Stage ll+lll  NSABP-C-07

NSABP-C-07: 5-FU/LV versus 5-FU/LV plus Oxaliplatin in Stage II/III Colon Cancer x 3 LV R Week FU LV FU 500 OHP852hr Rest Source: Wolmark N. Presentation. ASCO 2005.

NSABP-C-07 Opened: Closed: 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.

C-07 Accrual FULVFLOX Randomized Ineligible/Lost 1, , Analysis1,2071,200 Source: Wolmark N. Presentation. ASCO 2005.

C-07 Patient Characteristics AgeFULV %FLOX % < LocationFULV %FLOX % Left Colon Right Colon Sigmoid Multiple + Unk Positive NodesFULV %FLOX % ≥ Source: Wolmark N. Presentation. ASCO 2005.

GradeFULVFLOX 0-II III IV V Source: Wolmark N. Presentation. ASCO C-07 Overall Toxicity (%)

C-07 Sanofi-NCI Neurotoxicity Gr IP/D that do not interfere with function Gr IIP/D interfering with function, but not ADL Gr IIIP/D with pain or interference with ADL Gr IVPersistent P/D that are disabling or life-threatening Source: P = paresthesia; D = dysesthesia; ADL = activities of daily living

Grade ≥ 1 (All) Neurotoxicity (%) During Tx C-07 Sanofi-NCI Neurotoxicity Grade > 1 (All) Neurotoxicity (%) During Tx12 months Source: Wolmark N. Presentation. ASCO 2005.

C-07 Sanofi-NCI Neurotoxicity Grade III Neurotoxicity (%) During Tx12 months Source: Wolmark N. Presentation. ASCO 2005.

Oxaliplatin Protocol-Stipulated Cumulative Dose C mg/m 2 MOSAIC1,020 mg/m 2 Source: Wolmark N. Presentation. ASCO 2005.

73% received protocol-stipulated cumulative dose Percent of Full Dose Oxaliplatin/Cycle Source: Wolmark N. Presentation. ASCO 2005.

N FULV34 (2.7%) FLOX56 (4.5%) Source: Smith RE et al. Proc ASCO GI C-07 Bowel Wall Injury

C-07 Deaths During Treatment N FULV14 (1.1%) FLOX15 (1.2%) Source: Wolmark N. Presentation. ASCO 2005.

Proportion of patients % risk reduction p < HR: 0.79 [0.67 – 0.93] C-07 Disease-Free Survival Events3y DFS FLOX % FULV % Source: Wolmark N. Presentation. ASCO Years

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

Benefit from Oxaliplatin in NSABP-C-07 and MOSAIC Trials 3y DFSΔHR C %4.9%0.79 MOSAIC77.9%4.9%0.77 Sources: Wolmark N. Presentation. ASCO 2005; de Gramont A. Presentation. ASCO 2003.

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.