Prospective pooled analysis of four randomized trials investigating duration of adjuvant (adj) oxaliplatin-based therapy (3 vs 6 months {m}) for patients (pts) with high-risk stage II colorectal cancer (CC).

Abstract

3501 Background: 6m of oxaliplatin-based treatment is an option as adj chemotherapy for patients with high risk stage II CC (T4, inadequate nodal harvest, poorly differentiated, obstruction, perforation or vascular/perineural invasion). The IDEA collaboration showed shorter treatment duration to be appropriate for most pts with stage III colon cancer. The results of the 4 IDEA studies with stage II pts are presented here. Methods: A prospective, pre-planned pooled analysis of high-risk stage II patients from 4 concurrently conducted randomized phase III trials (SCOT, TOSCA, ACHIEVE-2, HORG) was performed to evaluate non-inferiority (NI) of 3m compared with 6m (ref) of adj FOLFOX/CAPOX (regimen preselected, not randomized). The primary endpoint was disease-free survival (DFS), NI was to be declared if the 2-sided 80% confidence interval (CI) for DFS hazard ratio (HR 3m v 6m) estimated by a stratified Cox model was below 1.2. 542 DFS events were required to provide 80% power to declare NI. NI was also examined within regimen, T4 (Yes v No) and inadequate nodal harvest (Yes v No) as pre-planned subgroups. Results: The primary analysis included 3273 randomised pts of which 1254 had FOLFOX and 2019 had CAPOX. There were 552 events and the median follow-up was 60.2 m. There was significantly less grade 3-5 toxicity with 3m treatment (p < .0001). The 5-year DFS rate was 80.7% and 84.0% for 3m and 6m treatment with an estimated DFS HR of 1.18 (80% CI:1.05-1.31, p for NI = 0.404). For CAPOX the estimated HR was 1.02 (80% CI: 0.88-1.17, p for NI = 0.087) and for FOLFOX the estimated HR was 1.42 (80% CI: 1.19-1.70, p for NI = 0.894). The test for interaction between duration and regimen was not statistically significant (p = .174 adjusted for multiple testing) but was stronger than that for the other subgroups examined. Conclusions: In the overall population non-inferiority for 3m adj treatment in pts with high-risk stage II CC was not shown. As with the stage III population the choice of adj regimen appears important (although this did not reach statistical significance) with a small difference in DFS between 3 and 6 m treatment if CAPOX is used. Clinical trial information: ISRCTN59757862.

Localised colon cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

“…It is also felt by the panel members that patients with high risk, patients with pT4 and/or <12 lymph nodes or accumulation of several intermediate risk factors, might be considered for the addition of oxaliplatin therapy based on a trend to an increased benefit, although this did not achieve statistical significance in the stage II high-risk subgroup analysis of the MOSAIC trial [I, B]. 72 For this high-risk population, the IDEA trial explored the optimal duration of the oxaliplatin-based adjuvant treatment, finding identical results to those reported for stage III patients, a non-proven non-inferiority for 3 months of treatment and there was a proven non-inferiority of CAPOX and inferiority of FOLFOX for 3 months when compared with 6 months of FOLFOX, 82 with all the limitations of these post hoc analyses as stated before. The presence of MSI/MMR in Annals of Oncology localised disease confers better prognosis and less benefit to adjuvant therapy so chemotherapy should be indicated with caution and always in combination with oxaliplatin 51e55 (see Figure 4 for integration of clinicopathological and molecular factors with therapeutic recommendations).…”

Clinical factors related to severe enterocolitis after adjuvant CAPOX for colorectal cancer: a retrospective analysis

“…Three months of CAPOX is replacing the 6 months of adjuvant FOLFOX for a considerable number of patients. More recent data also show a possible reduction in the length of adjuvant treatment in high-risk stage II patients [13]. Here, we describe the characteristics of eight patients who presented life-threatening enterocolitis after adjuvant CAPOX.…”

Adjuvant Therapies in Colon Cancer

“…In the overall population, 6 months was superior to 3 months, however, 3 months of CAPOX regimen was non-inferior to 6 months. There were 1254 patients with high risk stage II disease in the IDEA collaborative study (including TOSCA study) which investigated the optimal duration of adjuvant therapy [56]. Investigators concluded that 3 months of CAPOX may be non-inferior to 6 months in high risk stage II cancers, reflecting the finding in stage III disease.…”