Background

1. FLOX Effect In Subsets Defined by Significant Treatment Interaction Overall FLOX Treatment Effect National Surgical Adjuvant Breast and Bowel Project Male < 70 Female < 70 Group Pts Events FULV 587 222 FLOX 552 188 HR 0.87 (0.71-1.05), P = 0.15 Group Pts Events FULV 419 173 FLOX 455 137 HR 0.64 (0.51-0.80), P = 0.0001 Percent Alive and Disease-Free Male 70+ Female 70+ Group Pts Events HR (95% CI) P-value FULV 1209 483 FLOX 1200 412 0.81 (0.71-0.92) 0.0017 Percent Alive and Disease-Free DFS Group Pts Events FULV 91 38 FLOX 81 34 HR 0.99 (0.62-1.57), P = 0.97 Group Pts Events FULV 112 50 FLOX 112 53 HR 1.11 (0.76-1.64), P = 0.59 Number at Risk FULV 928 789 655 153 FLOX 971 848 693 162 Percent Recurrence-Free Group Pts Recur HR (95% CI) P-value FULV 1209 356 FLOX 1200 300 0.81 (0.69-0.94) 0.0062 Number at Risk FULV 953 828 700 172 FLOX 983 875 732 173 Male < 70 Female < 70 Group Pts Deaths FULV 587 145 FLOX 552 133 HR 0.95 (0.75-1.21), P = 0.70 Group Pts Deaths FULV 419 119 FLOX 455 94 HR 0.67 (0.51-0.88), P = 0.0035 Years Percent Alive OS Percent Alive Male 70+ Female 70+ Group Pts Deaths HR (95% CI) P-value FULV 1209 332 FLOX 1200 298 0.88 (0.75-1.03) 0.1173 Group Pts Deaths FULV 91 30 FLOX 81 28 HR 1.11 (0.66-1.85), P = 0.70 Group Pts Deaths FULV 112 38 FLOX 112 43 HR 1.22 (0.79-1.90), P = 0.37 Number at Risk FULV 1102 966 782 188 FLOX 1089 972 802 183 Male < 70 Female < 70 Group Pts Recurred FULV 587 164 FLOX 552 145 HR 0.91 (0.72-1.13), P = 0.39 Group Pts Recurred FULV 419 137 FLOX 455 103 HR 0.62 (0.48-0.80), P < 0.0001 Percent Recurrence-Free Male 70+ Female 70+ TTR Group Pts Recurred FULV 91 24 FLOX 81 22 HR 1.05 (0.59-1.87), P = 0.87 Group Pts Recurred FULV 112 31 FLOX 112 30 HR 1.08 (0.66-1.79), P = 0.76 Years 5-FU and leucovorin with or without oxaliplatin for adjuvant treatment of stage II and III colon cancer: Long-term follow-up of NSABP C-07 with survival analysis Greg Yothers, Michael J. O’Connell, Linda Colangelo, J. Phillip Kuebler, Samia Lopa, Michael P. Findlay, Thomas E. Seay, James N. Atkins, and Norman Wolmark Multivariate Cox Models Show Treatment Interaction with Age and Gender Background The primary analysis for C-07 showed improved disease-free survival at 3.5 yr median follow-up with the addition of oxaliplatin to 5-FU + LV (Kuebler et al, JCO 2007). Follow-up is now sufficient to report the secondary prospective endpoint overall survival. Methods From 2000 to 2002, patients with resected stage II or III colon cancer were randomized to 5-FU, 500 mg/m2 IV bolus weekly x 6; Leucovorin, 500 mg/m2 IV weekly x 6, each 8 week cycle x 3 (FULV), or same regimen with Oxaliplatin 85 mg/m2 IV on weeks 1, 3, and 5 of each cycle (FLOX). DFS events include recurrence, second primary cancer, and death. Other endpoints include time to recurrence (TTR) and overall survival (OS). Age was split at 70 for exploratory tests of interaction suggested by ACCENT analyses. HR < 1 favors FLOX. Conclusions • Improved DFS and TTR with FLOX are sustained through 7 yrs in the overall population. OS benefit overall with FLOX is not significant. • Exploratory analyses by age and gender require confirmation but suggest a robust effect for FLOX in female patients under age 70 on all endpoints. Clear benefit from FLOX in male patients or those over age 70 is not apparent and may not offset increased toxicity Results • 2,409 eligible pts with follow-up comprise the analysis. • Median follow-up is 7.05 years • 29% of patients are stage II, 46% 1-3 pos. nodes, 25% 4+ • 16% of patientswere age 70 or older at entry • 43% of patients were female • DFS and TTR were improved overall with FLOX • OS was not significantly different by arm overall • Significant age-FLOX interactions were observed for DFS and OS, but not TTR (Table) • Significant gender-FLOX interactions were observed for all endpoints (Table) • Within age-gender subsets, DFS, OS, and TTR were superior with FLOX among female patients < 70 • Grade 3+ neurotoxicity, nausea or vomiting, and dehydration was more frequent in FLOX patients regardless of age or gender Acknowledgements This work supported by grants from the National Cancer Institute and sanofi-aventis. We thank the membership of the NSABP, the staff of the NSABP Biostatistical and Operations Centers, and especially the trial participants without whom this research would not have been possible. ASCO GI Sunday Jan 24, 2010General Poster Session C Poster A123, Abstract 401