CRA3507 Background: FOLFOX is standard adjuvant therapy for stage III CC. Adding Cmab to FOLFOX benefits pts with metastatic CC WT KRAS tumors. N0147 assessed the potential benefit of Cmab added to FOLFOX. Methods: 21-56 days following resection and informed consent, KRAS status was centrally determined. Pts with wtKRAS CC were randomized to 12 biweekly cycles of oxaliplatin 85 mg/m2 d1, with leucovorin 400 mg/m2, 5FU 400 mg/m2 bolus IV, then 46-hr IV 5FU 2,400 mg/m2 on d1-2 (mFOLFOX6), without (arm A) or with Cmab (arm D) 250 mg/m2 d1&8, with Cmab at 400 mg/m2, cycle 1, d1. Primary endpoint was 3-yr disease free survival (DFS). Secondary endpoints included overall survival (OS) and toxicity. Planned accrual of 2,070 wtKRAS pts provided 90% power to detect hazard ratio (HR) of 1.33 with 2-sided α=0.05; with interim analyses after 25%, 50%, and 75% of planned events. Results: 1,760 wtKRAS pts (Arm A-858, Arm D-902) were enrolled at the time of closure; median follow-up on 1,624 pts is 15.9 months. Trial closed to accrual when preplanned interim analysis after 50% of planned events demonstrated no benefit to addition of Cmab. 3-yr DFS favored FOLFOX alone (HR 1.18, 95% CI 0.92-1.52; p=0.33). No benefit of Cmab was observed in any subgroups assessed. Any grade ≥ 3 AE, diarrhea, and failure to complete 12 cycles was significantly increased in arm D. Increased toxicity and greater differences in all outcomes were observed in pts aged ≥ 70 ( Table ). Conclusions: In this randomized phase III trial the addition of Cmab to mFOLFOX6 was of no benefit for pts with resected stage III wtKRAS CC. Supported by NIH Grant CA25224, Bristol-Myers Squibb, ImClone, Sanofi-Aventis, and Pfizer. [Table: see text] [Table: see text]

No abstract

No abstract

No abstract

No abstract

No abstract

No abstract

4010 Background: Prior studies suggested that older and younger pts with colon cancer receive similar benefit from IV fluoropyrimidine (FU) adjuvant (adj) therapy (rx). Combination and/or oral FU rx are increasingly given as adj rx. We sought to determine the impact of pts age <70 v ≥70 yrs on colon cancer recurrence and mortality from adj rx with these newer options. Methods: We used data from 10,499 pts <70 yrs and 2,170 pts ≥70 yrs in 6 phase III adj rx trials comparing IV FU to combinations with irinotecan, oxaliplatin or oral FU (capecitabine and UFT/LV) in stage II/III colon cancer from the ACCENT database. Endpoints were overall survival (OS; time to death), disease-free survival (DFS; time to recurrence or death), and time to recurrence (TTR; censoring at last follow-up). Cox models were stratified by age and adjusted for gender and stage; interaction testing was used to explore the differential benefit by age. Results: Approximately 75% of pts had stage III disease (74% age<70, 77% age≥70). OS, DFS, and TTR were statistically significantly improved for those in the experimental v control arms among pts <70 but not those >70 ( table ); the interaction between age and rx was statistically significant for all endpoints (p=0.01 for OS, DFS, and TTR). These results were consistent whether experimental rx was oxaliplatin-based, irinotecan-based or oral FU. Deaths in first 6 month of adj rx were not statistically significantly different between experimental and control arm. Conclusions: Our results show conclusively that pts >70 do not receive the same benefit from combination and/or oral FU as those <70. Any benefit, if present, compared to IV FU/LV would not be clinically meaningful. Outcomes of experimental (combination or oral FU) vs control (IV 5-FU) by treatment and age [Table: see text] [Table: see text]