1 / 21

ESMO/ECCO Presidential Session III

NO16968: XELOXA Adjuvant Treatment with Capecitabine and Oxaliplatin (XELOX) in Stage III Colon Cancer. ESMO/ECCO Presidential Session III D. Haller, J. Tabernero, J. Maroun, F. de Braud, T. Price, E. Van Cutsem, M. Hill, F. Gilberg, K. Rittweger, H.-J. Schmoll. Rationale for XELOXA trial.

amos
Download Presentation

ESMO/ECCO Presidential Session III

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. NO16968: XELOXAAdjuvant Treatment with Capecitabine and Oxaliplatin (XELOX) in Stage III Colon Cancer ESMO/ECCO Presidential Session III D. Haller, J. Tabernero, J. Maroun, F. de Braud, T. Price, E. Van Cutsem, M. Hill, F. Gilberg, K. Rittweger,H.-J. Schmoll

  2. Rationale for XELOXA trial • In 2002, when planning the study, the standard of care for adjuvant treatment of colon cancer was bolus 5-FU/LV (either Mayo Clinic or Roswell Park regimen) • Based on upcoming results of X-ACT trial, capecitabine was expected to be at least equivalent to bolus 5-FU/LV in stage III colon cancer • Two large trials were ongoing investigating the additional benefit of oxaliplatin to bolus or infusional 5-FU/LV (NSABP C-07 and MOSAIC)

  3. Rationale for XELOXA trial • In order to investigate oral fluoropyrimidines plus oxaliplatin, based on the X-ACT trial, capecitabine was chosen as a partner with oxaliplatin vs the standard of care at the time (bolus 5-FU/LV) • XELOXA became the third of 3 parallel conducted studies (NSABP C-07, MOSAIC and XELOXA) investigating the role of oxaliplatin in adjuvant treatment of colon cancer • In contrast to NSABP C-07 and MOSAIC, which included stage II and III patients, XELOXA investigated only stage III given the preliminary results of the X-ACT trial (stage III disease only)

  4. Adjuvant XELOX vs 5-FU/LV: NO16968 (XELOXA) Phase III trial RANDO MIS ATION XELOX (6 months) capecitabine 1000mg/m2 bid d1–14 oxaliplatin130mg/m2 d1 q3w8 cycles n=944 Chemo/radiotherapy-naive stage III colon ≤8 weeks since resectionN=1886 Bolus 5-FU/LV (6 months) Mayo Clinic [n=664]orRoswell Park [n=278] n=942 • Primary endpoint: superiority of DFS • Secondary endpoints: RFS, OS, tolerability

  5. Eligibility • 18 years old, ECOG 1 • Stage III colon carcinoma, 1 positive lymph node • Randomised 8 weeks after surgery • Informed consent • Normal or mild renal impairment • No seizures, CNS disorders, psychiatric disability, cardiac disease (CHF, symptomatic CAD or arrhythmias), or MI 12 months • Normal neutrophils, platelets, creatinine, bilirubin, ALAT, ASAT, alkaline phosphatase

  6. Stratification factors • Patients stratified by • geographic region • number of lymph nodes involved (≤3 vs ≥4) • baseline CEA (normal vs abnormal) • 5-FU/LV regimen (Mayo vs Roswell Park) • number of lymph nodes sampled per geographical region

  7. Patient demographics ITT population

  8. Safety Schmoll et al. JCO 2007

  9. Cross-trial comparison with MOSAIC Schmoll et al. JCO 2007*MOSAIC trial: André et al. NEJM 2004

  10. Efficacy Results

  11. Primary endpoint met:superior DFS with XELOX XELOX 1.0 5-FU/LV 0.8 0.6 0.4 HR=0.80 (95% CI: 0.69–0.93)p=0.0045 0.2 0.0 0 1 2 3 4 5 6 Years ITT population

  12. 3-year DFS:benefit with XELOX maintained and increased over time 3-yearDFS XELOX 70.9% 1.0 5-FU/LV 66.5% 0.8 Δ at 3 years: 4.5% 0.6 0.4 0.2 0.0 0 1 2 3 4 5 6 Years ITT population

  13. 4-year DFS:benefit with XELOX maintained and increased over time 3-yearDFS 4-yearDFS XELOX 70.9% 68.4% 1.0 5-FU/LV 66.5% 62.3% 0.8 Δ at 3 years: 4.5% 0.6 Δ at 4 years: 6.1% 0.4 0.2 0.0 0 1 2 3 4 5 6 Years ITT population

  14. 5-year DFS:benefit with XELOX maintained and increased over time 3-yearDFS 4-yearDFS 5-yearDFS XELOX 70.9% 68.4% 66.1% 1.0 59.8% 5-FU/LV 66.5% 62.3% 0.8 Δ at 3 years: 4.5% 0.6 Δ at 4 years: 6.1% Δ at 5 years:6.3% 0.4 0.2 0.0 0 1 2 3 4 5 6 Years ITT population

  15. DFS across stratification factors Favours XELOX Favours 5-FU n CI HR All 1886 0.69–0.93 0.80 ≤3 1222 0.59–0.90 0.73 Positive lymph nodes ≥4 664 0.71–1.11 0.89 Abnormal 140 0.56–1.32 0.86 CEA baseline value Normal 1724 0.66–0.92 0.78 Mayo 1331 0.64–0.92 0.77 5-FU/LV regimen Roswell 555 0.64–1.17 0.87 2 0.2 0.4 0.6 1 3 4 5 HR ITT population

  16. Superior RFS with XELOX(excludes all non-cancer-related mortality) 3-yearRFS 4-yearRFS 5-yearRFS 1.0 XELOX 72.1% 69.7% 67.8% 60.9% 5-FU/LV 67.5% 63.3% 0.8 Δ at 3 years: 4.6% 0.6 Δ at 4 years: 6.4% Δ at 5 years:6.9% 0.4 0.2 HR=0.78 (95% CI: 0.67–0.92)p=0.0024 0.0 0 1 2 3 4 5 6 Years ITT population

  17. Trend to improved OS with XELOX 5-yearOS 1.0 XELOX 77.6% 5-FU/LV 74.2% 0.8 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

  18. Cross-trial comparison of MOSAICand XELOXA: OS in stage III disease 1.0 1.0 XELOXA(57 mo) MOSAIC1(81.9 mo) 0.8 0.8 0.6 0.6 XELOX FOLFOX4 5-FU/LV LV5FU2 0.4 0.4 0 0 2 4 6 2 4 6 8 8 Years Years ITT population 1. André et al. JCO 2009

  19. Cross-trial comparison of MOSAICand XELOXA: OS in stage III disease 5-yr OS 6-yr OS NO16968 (XELOXA)* 77.6% – XELOX (n=944) 1.0 MOSAIC1** FOLFOX4 (n=672) – 72.9% 0.8 0.6 0.4 0 1 2 3 4 5 6 7 8 Years *Median observation time: 57.0 months **Median follow-up: 81.9 months ITT population 1.André et al. JCO2009

  20. NO16968 (XELOXA): conclusions • Efficacy • XELOX significantly improves DFS and RFS compared with bolus 5-FU/LV • trend to improved OS with XELOX; follow-up ongoing • Ease of administration • fewer study visits, no pumps or catheters • Favourable safety profile • XELOX is a new option and a new standard for patients with stage III colon cancer

  21. Thank you • To the 1886 patients and their families • To the participating 226 centres and investigators • To the nurses and study coordinators • To the NO16968 (XELOXA) Steering Committee • And everybody else who made this contribution to the advancement of patient care possible

More Related