SO-22 Clinical Classification-Based Evaluation of Adjuvant Therapy with Oxaliplatin in Stage II Colon Cancer

Standard adjuvant treatments for stage III colon cancer (CC) are mFOLFOX6 and CAPOX. Adjuvant treatment is not established in stage II CC where leucovorin-5FU (FU) has a limited efficacy and oxaliplatin (OX) may have some benefit in high-risk (HR) stage II CC. The definition of HR remains controversial. New clinical prognostic factors have been described such as sidedness. We performed a pooled analysis of the two studies, MOSAIC and NSABP C-07, to build a new clinical classification and reevaluate FUOX as adjuvant therapy. We pooled 1595 stage II CC pts. Baseline characteristics were compared using χ2 and t-test. Kaplan-Meier analyses and (un)adjusted Cox models were used. We performed (uni)multivariate analyses of clinical factors to build a new clinical score to better identify prognostic groups. Available variables were T stage, gender, primary tumor side, PS, differentiation, BMI, age, obstruction/perforation, number of examined lymph nodes. MSI was separately analyzed. The new score was validated using pairwise comparisons in 573-stage II CC pts included in the AVANT study. FU and FUOX were compared in the whole population and then in the low-risk (LR) and HR (T4 or < 10 examined nodes or perforation: old definition) groups. Then, we evaluated the effect of OX in each new prognostic subgroup. Outcomes were OS and time to recurrence (TTR). Prognostic factors were gender, age, sidedness, T stage and obstruction/perforation in univariate analyses. With backward selection in multivariate analysis, T stage was removed (44% of T4 pts had obstruction/perforation). The new scoring system defined three well-separated prognostic subgroups. 5-year survival using old definition was LR 91.2% (N=896) and HR 87.9% (N=689). With the new score, 5-year OS was LR (N=1049) 91.4%, intermediate risk (IR) (N=318) 89.5% and HR (N=228) 81.7% and pairwise comparisons were significant. 10-year OS in the pooled study were: LR 85.2%, IR 75.7%, HR 61.3%. The scoring system was validated in the AVANT study. 5-year OS were similar to the learning sample: LR 93.7%, IR 86.5%, HR 83.5%. In the pooled analysis, 797 pts received FU, 798 FUOX and pts characteristics were well-balanced. No OX benefit was observed in the global population nor in the HR or LR groups (old definition), hazard ratio in HR was 0.86 (p=0.349), LR 1.17 (p=0.338). Comparing FU vs FUOX, according to new-risk groups, 5-year OS were: LR 90.8% vs 91.9%, IR 91.6% vs 87.3%, HR 83.0% vs 80.3%, hazard ratios were 0.96 (p=0.789), 0.98 (p=0.917), 1.32 (p=0.204), respectively and 5-year TTR FU vs FUOX were: LR 87.6% vs 87.8%, IR 83.8% vs 88.4% and HR 71.6% vs 77.7%, hazard ratios were 1.01 (p=0.927), 1.25 (p=0.512), 0.80 (p=0.318), respectively. Our clinical scoring may help to design new trials especially in the high-risk group. There was no benefit of OX in our newly defined subgroups. OX is not the standard of care in adjuvant therapy of stage II CC based on clinical factors. Further studies should focus on new biomarkers like circulating tDNA to better identify the risk and the potential benefit of adjuvant therapy.