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Background

Phase III Trial of Capecitabine + Oxaliplatin vs Bolus 5-FU/LV in Stage III Colon Cancer (NO16968): Impact of Age on DFS and OS. D. Haller, 1 J. Cassidy, 2 J. Tabernero, 3 J. Maroun, 4 F. de Braud, 5 T. Price, 6 E. Van Cutsem, 7 M. Hill, 8 F. Gilberg, 9 H-J. Schmoll 10

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Background

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  1. Phase III Trial of Capecitabine + Oxaliplatin vs Bolus 5-FU/LV in Stage III Colon Cancer (NO16968): Impact of Age on DFS and OS D. Haller,1 J. Cassidy,2 J. Tabernero,3 J. Maroun,4 F. de Braud,5T. Price,6 E. Van Cutsem,7 M. Hill,8 F. Gilberg,9 H-J. Schmoll10 1University of Pennsylvania, Philadelphia, USA; 2Glasgow University, Glasgow, Scotland; 3Vall d'Hebron University Hospital, Barcelona, Spain; 4Ottawa Regional Cancer Centre, Ottawa, Canada; 5Istituto Europeo di Oncologia, Milan, Italy; 6The Queen Elizabeth Hospital, Adelaide, Australia; 7University Hospital Gasthuisberg, Leuven, Belgium; 8Maidstone Hospital, Maidstone, UK; 9Hoffmann-La Roche, Basel, Switzerland; 10Martin Luther University, Halle, Germany

  2. Adjuvant 5-FU/LV demonstrated benefit in older patients compared with surgery alone1 Oral capecitabine is at least equivalent to bolus 5-FU/LV for disease-free survival (DFS) and overall survival (OS) as adjuvant therapy in patients with stage III colon cancer2 Older patients (≥70 years) treated with capecitabine also showed improved outcomes vs. 5-FU/LV (X-ACT)2 Recent data from the MOSAIC trial and ACCENT database demonstrated that newer adjuvant regimens (e.g. oxaliplatin combinations) were not associated with significant efficacy benefits vs. 5-FU/LV in patients ≥65 years compared with younger patients3,4 Background 1. Sargent et al. NEJM 2001;345:1091–1097; 2. Twelves et al. NEJM 2005;352:2696–2704 3. André et al. J Clin Oncol 2009;27:3109–3116; 4. McCleary et al. ASCO 2009 (poster 4010)

  3. MOSAIC: DFS by age3 • MOSAIC trial demonstrated efficacy of FOLFOX4 vs. LV5FU2 is not maintained in patients ≥65 years Prognostic factor (n) Hazard ratio (95% CI) Overall Age ≥65 years (n=463) <65 years (n=884) 0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 FOLFOX4 better LV5FU2 better 3. André et al. J Clin Oncol 2009;27:3109–3116

  4. ACCENT: efficacy not maintained in patients ≥70 years of age in overall population4 *Values <1 favor experimental arm (oxaliplatin-based regimens) 4. McCleary et al. ASCO 2009 (poster 4010)

  5. ACCENT: efficacy of oxaliplatin-based (MOSAIC/C-07) combinations by age4 *Values <1 favor experimental arm (oxaliplatin-based regimens) 4. McCleary et al. ASCO 2009 (poster 4010)

  6. NO16968 (XELOXA): trial design5 Chemo/radiotherapy-naïve stage III colon cancer ≤8 weeks since resection (n=1886) RANDOMIZATION n=944 n=942 XELOX (6 months) capecitabine 1000 mg/m2 bid d1–14 oxaliplatin130 mg/m2 d1 q3w8 cycles Bolus 5-FU/LV (6 months) Mayo Clinic (n=664)orRoswell Park (n=278) 5. Haller D, et al. Eur J Cancer Suppl 2009;7:4(Abst 5LBA)

  7. NO16968 (XELOXA): patient demographics

  8. NO16968 (XELOXA) primary endpoint met: superior DFS with XELOX and benefit maintained and increased over time 3-yearDFS 4-yearDFS 5-yearDFS 1.0 70.9% 68.4% 66.1% 62.3% 59.8% 66.5% 0.8 XELOX Δ at 3 years: 4.5% 0.6 5-FU/LV Δ at 4 years: 6.1% Δ at 5 years:6.3% 0.4 0.2 HR=0.80 (95% CI: 0.69–0.93)p=0.0045 0.0 Years 0 1 2 3 4 5 6 ITT population

  9. NO16968 (XELOXA): trend toward improved OS with XELOX 5-yearOS 1.0 77.6% 74.2% 0.8 XELOX 5-FU/LV 0.6 Δ at 5 years:3.4% 0.4 0.2 HR=0.87 (95% CI: 0.72–1.05)p=0.1486 0.0 0 1 2 3 4 5 6 Years ITT population

  10. NO16968 (XELOXA): subgroup analysis Survival outcomes by age – analysis performed to: • Compare with data presented from ACCENT and MOSAIC • Assess treatment effects of XELOX vs. 5-FU/LV in patients by age: • ≥65 (planned) and ≥70 years (unplanned) • Determine if findings from ACCENT meta-analysis also apply to XELOX regimen • Determine relapse-free survival (RFS) overall and according to age

  11. NO16968 (XELOXA): subgroup analysis of DFS by age *Multiple Cox regression This non-significant p-value indicates that XELOX efficacy is positive, irrespective of age ITT population

  12. NO16968 (XELOXA): subgroup analysis of OS by age *Multiple Cox regression This non-significant p value indicates that XELOX efficacy is positive, irrespective of age ITT population

  13. NO16968 (XELOXA): subgroup analysis of RFS by age ITT population

  14. Comparison with ACCENT analysis *Values <1 favor oxaliplatin-based therapy vs. 5-FU/LV; †Data for oxaliplatin-based regimens 4. McCleary et al. ASCO 2009 (poster 4010)

  15. NO16968 (XELOXA): safety by age *Includes granulocytopenia Safety population

  16. XELOX results in superior DFS compared with bolus 5-FU/LV as adjuvant treatment for patients with stage III colon cancer These findings confirm the benefits previously demonstrated with the addition of oxaliplatin to 5-FU in stage III patients Efficacy benefits are maintained in patients ≥65 and ≥70 years in contrast to results from ACCENT and MOSAIC in which no significant benefit is shown with FOLFOX in this age group: reasons for this apparent difference are unknown OS data thus far indicate a trend toward superior survival with XELOX XELOX is an effective adjuvant therapy and should be considered for all eligible patients, without an arbitrary upper age limit NO16968 (XELOXA): conclusions

  17. Thank you to the: 1886 patients and their families 226 participating centers and investigators nurses and study coordinators NO16968 (XELOXA) Steering Committee others who made this contribution to the advancement of patient care possible Acknowledgments

  18. Sargent et al. NEJM 2001;345:1091–1097 Twelves et al. NEJM 2005;352:2696–2704 André et al. J Clin Oncol 2009;27:3109–3116 McCleary et al. J Clin Oncol 2009;27(15S):4010 Haller D, et al. Eur J Cancer Suppl 2009;7:4(Abst 5LBA) References

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